Abstract
Several animal species, mostly rodents, were described to exhibit spontaneously diabetes mellitus on a hereditary basis. These findings were highly appreciated with the expectation to get more insight into the pathogenesis of diabetes in humans. During the last few years since the discovery of leptin (Zhang et al. 1994) and its downstream signal transduction cascade (Friedman and Halaas 1998), tremendous new insight of the genetics of diabetic and obese animal disease models was derived. Up to now, at least six genetically diabetic animal models exhibit defects in the leptin pathway: the ob mutation in the mouse resulted in leptin deficiency. The db mutation in the mouse and the cp and fa mutations in the rat are different mutations of the leptin receptor gene. The fat mutation in the mouse results in a biologically inactive carboxypeptidase E, which processes the prohormone conversion of POMC into α-MSH, which activates the hypothalamic MC4 receptor. Finally the Agouti yellow (y) mouse exhibit a ubiquitous expression of the Agouti protein which represents an antagonist of the hypothalamic MC4 receptor.
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References and Further Reading
General Considerations
Brunk R (1971) Spontandiabetes bei Tieren. In: Dörzbach E (ed) Handbook of experimental pharmacology vol 32/1. Insulin. Springer, Berlin/Heidelberg/New York, pp 203–272
Friedman JF, Halaas JL (1998) Leptin and the regulation of body weight in mammals. Nature 395:763–770
Herberg L, Coleman DL (1977) Laboratory animals exhibiting obesity and diabetes syndromes. Metabolism 26:59–99
Herberg L, Berger M, Buchanan KD, Gries FA, Kern H (1976) Tiermodelle in der Diabetesforschung: metabolische und hormonelle Besonderheiten. Z Versuchstierk 18:91–105
Shafrir E (1992) Animal models of non-insulin-dependent diabetes. Diabetes/Metab Rev 8:179–208
Velasquez MT, Kimmel PL, Michaelis OE IV (1990) Animal models of spontaneous diabetic kidney disease. FASEB J 4:2850–2859
Zhang Y, Proenca R, Maffei M, Barone M, Leopold L, Friedman JF (1994) Positional cloning of the mouse obese gene and its human homologue. Nature 372:425–432
Spontaneously Diabetic Rats: BB Rat
Berg S, Dunger A, Vogt L, Schmidt S (1997) Circadian variations in blood pressure and heart rate in diabetes prone and resistant rat strains compared with spontaneously hypertensive rats. Exp Clin Endocrinol Diabetes 105(Suppl 2):7–9
Ellerman K, Wroblewski M, Rabinovitch A, Like A (1993) Natural killer cell depletion and diabetes mellitus in the BB/Wor rat. Diabetologia 36:596–601
Gottlieb PA, Berrios JP, Mariani G, Handler ES, Greiner D, Mordes JP, Rossini AA (1990) Autoimmune destruction of islets transplanted into RT6-depleted diabetes-resistant BB/Wor rats. Diabetes 39:643–645
Hao L, Chan SM, Lafferty KJ (1993) Mycophenolate mofetil can prevent the development of diabetes in BB rats. Ann N Y Acad Sci 969:328–332
Klöting I, Vogt L (1991) BB/O(TTAWA)K(ARLSBURG) rats: features of a subline of diabetes prone BB rats. Diabetes Res 18:79–87
Kolb H, Burkart V, Appels B, Hanenberg H, Kantwerk-Funke G, Kiesel U, Funda J, Schraermeyer U, Kolb-Bachofen V (1990) Essential contribution of macrophages to islet cell destruction in vivo and in vitro. J Autoimmun 3(Suppl 1):117–120
Lee KU, Pak CY, Amano K, Yoon JW (1988) Prevention of lymphocytic thyroiditis and insulitis in diabetes-prone BB rats by the depletion of macrophages. Diabetologia 31:400–402
Lefkowith J, Schreiner G, Cormier J, Handler ES, Driscoll HK, Greiner D, Mordes JP, Rossini AA (1990) Prevention of diabetes in the BB rat by essential fatty acid deficiency. J Exp Med 171:729–743
Like AA, Butler L, Williams RM, Appel MC, Weringer EJ, Rossini AA (1982) Spontaneous autoimmune diabetes mellitus in the BB rat. Diabetes 31(Suppl 1):7–11
Nakhooda AF, Like AA, Chappel CI, Murray FT, Marliss EB (1977) The spontaneously diabetic Wistar rat; metabolic and morphologic studies. Diabetes 26:100–112
Nakhooda AF, Like AA, Chappel CI, Wei CN, Marliss EB (1978) The spontaneously diabetic Wistar rat (the “BB” rat). Studies prior to and during development of the overt syndrome. Diabetologia 14:199–207
Oschilewski U, Kiesel U, Kolb H (1985) Effect of cyclosporin A on low-dose streptozotocin diabetes in mice. Diabetes 34:197–199
Papaccio G, Mezzogiorno V (1989) Morphological aspects of glucagon and somatostatin islet cells in diabetic bio breeding and low-dose streptozotocin-treated Wistar rats. Pancreas 4:289–294
Pipeleers D, Pipeleers-Marichal M, Markholst H, Hoorens A, Klöppel G (1991) Transplantation of purified islet cells in diabetic BB rats. Diabetologia 34:390–396
Sima AAF (1984) Neuropathic and ocular complications in the BB-Wistar rat. In: Shafrir R, Reynold A (eds) Lesson from diabetes. John Libby’s, London, pp 447–453
Solomon SS, Deaton J, Harris G, Smoake JA (1989) Studies of insulin resistance in the streptozotocin diabetic and BB rat: activation of low Km cAMP phosphodiesterase by insulin. Am J Med Sci 297:372–376
Velasquez MT, Kimmel PL, Michaelis OE (1990) Animal models of spontaneous diabetic kidney disease. FASEB J 4:2850–2859
Spontaneously Diabetic Rats: WBN/Kob Rat
Koizumi M, Shimoda I, Sato K, Shishido T, Ono T, Ishizuka J, Toyota T, Goto Y (1989) Effects of CAMOSTAT on development of spontaneous diabetes in the WBN/Kob rats. Biomed Res 10(Suppl 1):45–50
Nakama K, Shichinohe K, Kobayashi K, Naito K, Ushida O, Yasuhara K, Zobe M (1985) Spontaneous diabetes-like syndrome in WBN/Kob rats. Acta Diabetol Lat 122:335–342
Shimoda I, Koizumi M, Shimosegawa T, Shishido T, Ono T, Sato K, Ishizuka J, Toyota T (1993) Physiological characterization of spontaneously developed diabetes in male WBN/Kob rat and prevention of development of diabetes by chronic oral administration of synthetic trypsin inhibitor (FOY-305). Pancreas 8:196–203
Tsuchitani M, Saegusa T, Narama I, Nishikawa T, Gonda T (1985) A new diabetic strain of rat (WBN/Kob). Lab Anim 19:200–207
Yagihashi S, Wada RI, Kamijo M, Nagai K (1993) Peripheral neuropathy in the WBN/Kob rat with chronic pancreatitis and spontaneous diabetes. Lab Invest 68:296–307
Spontaneously Diabetic Rats: Cohen Diabetic Rat
Cohen AM, Teitelbaum A, Saliternik R (1972) Genetics and diet as factors in the development of diabetes mellitus. Metabolism 21:235–240
Velasquez MT, Kimmel PL, Michaelis OE (1990) Animal models of spontaneous diabetic kidney disease. FASEB J 4:2850–2859
Spontaneously Diabetic Rats: Goto–Kakizaki Rat
Avignon A, Yamada K, Zhou X (1996) Chronic activation of protein kinase C in soleus muscles and other tissues of insulin-resistant type II diabetic Goto–Kakizaki (GK), obese/aged and obese/Zucker rats. A mechanism for inhibiting glycogen synthesis. Diabetes 45:1396–1404
Begum N, Ragiola L (1998) Altered regulation of insulin signaling components in adipocytes of insulin-resistant type II diabetic Goto–Kakizaki rats. Metabolism 47:54–62
Goto Y, Kakizaki M, Masaki N (1975) Spontaneous diabetes produced by selective breeding of normal Wistar rats. Proc Jpn Acad 51:80–85
Portha B, Serradas P, Bailbe D (1991) β cell insensitivity in the GK rat, a spontaneous non-obese model for type II diabetes. Diabetes 40:486–491
Villar-Palsi C, Farese RV (1994) Impaired skeletal muscle glycogen synthase activation by insulin in the Goto–Kakizaki (G/K) rat. Diabetologia 37:885–888
Spontaneously Diabetic Rats: Zucker-Fatty Rat
Abadie JM, Wright B, Correa G, Browne ES, Porter JR, Svec F (1993) Effect of dihydro-epiandrosterone on neurotransmitter levels and appetite regulation of the obese Zucker rat. Diabetes 42:662–669
Alamzadeh R, Slonim AE, Zdanowicz MM (1993) Modification of insulin resistance by diazoxide in obese Zucker rats. Endocrinology 133:705–712
Bray GA (1977) The Zucker-fatty rat: a review. Fed Proc 36:148–153
Clark JB, Palmer CJ, Shaw WN (1983) The diabetic Zucker fatty rat. Proc Soc Exp Biol Med 173:68–75
Fujiwara T, Yoshioka S, Yoshioka T, Ushiyama I, Horikoshi H (1988) Characterization of new oral antidiabetic agent CS-045. Studies in KK and ob/ob mice and Zucker fatty rats. Diabetes 37:1549–1558
Galante P, Maerker E, Scholz R, Rett K, Herberg L, Mosthaf L, Häring HU (1994) Insulin-induced translocation of GLUT 4 in skeletal muscle of insulin-resistant Zucker rats. Diabetologia 37:3–9
Kasim SE, Elovson J, Khilnani S, Almario RU, Jen KLC (1993) Effect of lovastatin on the secretion of very low density lipoproteins and apolipoprotein B in the hypertriglyceridemic Zucker obese rat. Atherosclerosis 104:147–152
Kava R, Greenwoof MRC, Johnson PR (1990) New rat models of obesity and type II diabetes-Zucker (fa/fa) rat. Ilar News 32:4–8
McCaleb ML, Sredy J (1992) Metabolic abnormalities of the hyperglycemic obese Zucker rat. Metabolism 41:522–525
Shafrir E (1992) Animal models of non-insulin-dependent diabetes. Diabetes/Metab Rev 8:179–208
Stern J, Johnson PR, Greenwood RC, Zucker LM, Hirsch J (1972) Insulin resistance and pancreatic insulin release in the genetically obese Zucker rat. Proc Soc Exp Biol Med 139:66–69
Stern JS, Johnson PR, Batchelor BR, Zucker LM, Hirsch J (1975) Pancreatic insulin release and peripheral tissue resistance in Zucker obese rats fed high- and low-carbohydrate diets. Am J Physiol 228:543–548
Vasselli JR, Flory T, Fried KS (1987) Insulin binding and glucose transport in adipocytes of acarbose-treated Zucker lean and obese rats. Int J Obes 11:71–75
Yoshioka S, Nishino H, Shiraki T, Ikeda K, Koike H, Okuno A, Wada M, Fujiwara T, Horikoshi H (1993) Antihypertensive effects of CS-045 treatment in obese Zucker rats. Metabolism 42:75–80
Zucker LM (1965) Hereditary obesity in the rat associated with hyperlipidemia. Ann N Y Acad Sci 131:447–458
Zucker LM, Antoniades HN (1972) Insulin and obesity in the Zucker genetically obese rat “Fatty”. Endocrinology 90:1320–1330
Spontaneously Diabetic Rats: Zucker Diabetic Fatty Rat (Zdf/Drt-Fa)
Lee Y, Hirose H, Ohneda M, Johnson JH, McGarry JD, Unger RH (1994) β-cell lipotoxicity in the pathogenesis of noninsulin-dependent diabetes mellitus of obese rats: impairment in adipocytes-β-cell relationships. Proc Natl Acad Sci 91:10878–10882
Peterson RG, Shaw WN, Neel M-AN, Little LA, Eicheberg J (1990) Zucker Diabetic Fatty rat as a model for non-insulin dependent diabetes mellitus. ILAR News 32:16–19
Spontaneously Diabetic Rats: Wdf/Ta-Fa Rat
Griffen SC, Wang J, German MS (2001) A genetic defect in beta-cell gene expression segregates independently from the fa locus in the ZDF rat. Diabetes 50:63–68
Ikeda H, Shino A, Matsuo T, Iwatsuka H, Suzuoki Z (1981) A new genetically obese-hyperglycemic rat (Wistar fatty). Diabetes 30:1045–1050
Kava RA, West DB, Lukasik VA, Greenwood MRC (1989) Sexual dimorphism of hyperglycemia and glucose tolerance in Wistar fatty rats. Diabetes 38:159–163
Kava RA, Peterson RG, West DB, Greenwood MRC (1990) New rat models of obesity and type II diabetes-Wistar diabetic fatty rat. Ilar News 32:9–13
Kobayashi M, Iwanshi M, Egawa K, Shigeta Y (1992) Pioglitazone increases insulin sensitivity by activating insulin receptor kinase. Diabetes 41:476–483
Madar Z, Omusky Z (1991) Inhibition of intestinal α-glucosidase activity and postprandial hyperglycemia by α-glucosidase inhibitors in fa/fa rats. Nutr Res 11:1035–1046
Peterson RG, Little LA, Neel MA (1990) WKY fatty rat as a model of obesity and non-insulin dependent diabetes mellitus. Ilar News 32:13–15
Sugiyama Y, Taketomi S, Shimura Y, Ikeda H, Fujita T (1990a) Effects of pioglitazone on glucose and lipid metabolism in Wistar fatty rats. Arzneim Forsch/Drug Res 40:263–267
Sugiyama Y, Shimura Y, Ikeda H (1990b) Effects of pioglitazone on hepatic and peripheral insulin Wistar fatty rats. Arzneim Forsch/Drug Res 40:436–440
Velasquez MT, Kimmel PL, Michaelis OE IV (1990) Animal models of spontaneous diabetic kidney disease. FASEB J 4:2850–2859
Spontaneously Diabetic Rats: OLETF Rat
Aizawa T, Taguchi N, Sato Y, Nakabayashi T, Kobuchi H, Hidaka H, Nagasawa T, Ishihara F, Itoh N, Hashizume K (1995) Prophylaxis of genetically determined diabetes by diazoxide: a study in a rat model of naturally occurring obese diabetes. J Pharmacol Exp Ther 275:194–199
Ishida K, Mizuno A, Sano T, Shima K (1995) Which is the primary etiologic event in Otsuka Long-Evans Tokushima fatty rats, a model of spontaneous non-insulin-dependent diabetes mellitus, insulin resistance, or impaired insulin secretion? Metabolism 44:940–945
Kawano K, Hirashima T, Mori S, Kurosumi M, Saitoh Y (1991) A new rat strain with non-insulin dependent diabetes mellitus, “OLETF”. Rat News Lett 25:24–26
Kawano K, Hirashima T, Mori S, Saitoh YA, Kurosumi M, Natori T (1992) Spontaneous long-term hyperglycemic rat with diabetic complications. Otsuka Long-Evans Tokushima fatty (OLETF) strain. Diabetes 41:1422–1428
Spontaneously Diabetic Rats: ESS-Rat
Dumm CLAG, Semino MC, Gagliardino JJ (1990) Sequential changes in pancreatic islets of spontaneously diabetic rats. Pancreas 5:533–539
Herberg L, Coleman DL (1977) Laboratory animals exhibiting obesity and diabetes syndromes. Metabolism 26:59–99
Tarrés MC, Martínez SM, Liborio MM, Rabasa SL (1981) Diabetes mellitus en una línea endocrinada de rata. Mendeliana 5:39–48
Spontaneously Diabetic Rats: Obese SHR Rat
Friedman JE, Ishizuka T, Liu S, Farrell CJ, Bedol D, Koletsky RJ, Kaung HL, Ernsberger P (1997) Reduced insulin receptor signaling in the obese spontaneously hypertensive Koletsky rat. Am J Physiol Endocrinol Metab 273:E1014–E1023
Koletsky S (1973) Obese spontaneous hypertensive rats – a model for study of arteriosclerosis. Exp Mol Pathol 19:53–60
Koletsky S (1975) Pathologic findings and laboratory data in a new strain of obese hypertensive rats. Am J Pathol 80:129–142
Russell JC, Graham S, Hameed M (1994) Abnormal insulin and glucose metabolism in the JCR:LA-corpulent rat. Metabolism 43:538–543
Velasquez MT, Kimmel PL, Michaelis OE (1990) Animal models of spontaneous diabetic kidney disease. FASEB J 4:2850–2859
Spontaneously Diabetic Rats: SHR/N-cp Rat
Adamo M, Shemer J, Aridor M, Dixon J, Carswell N, Bhathena SJ, Michaelis OE IV, LeRoith D (1989) Liver insulin receptor tyrosine kinase activity in a model of type II diabetes mellitus and obesity. J Nutr 119:484–489
Hansen CT (1983) Two new congenic rat strains for nutrition and obesity research. Fed Proc 42:573
Hansen CT (1988) The development of the SRH/N- and LA/N-cp (corpulent) congenic rat strains. In: Hansen CT, Michaelis OE IV (eds) New models of genetically obese rats for studies in diabetes, heart disease, and complications of obesity. Summaries of workshop papers and current bibliography. National Institutes of Health, Bethesda, pp 7–10
McCune SA, Baker PB, Stills HF (1990) SHHF/Mcc-cp rat: a model of obesity, non-insulin-dependent diabetes, and congestive heart failure. Ilar News 32:23–27
Michaelis OE, Hansen CT (1990) The spontaneous hypertensive/NIH corpulent rat: a new rodent model for the study of non-insulin dependent diabetes mellitus and its complications. Ilar News 32:19–22
Michaelis OE, Patrick DH, Hansen A, Canry JJ, Werner RM, Carswell N (1986) Spontaneous hypertensive/NIH-corpulent rat. An animal model for insulin-independent diabetes mellitus (type II). Am J Pathol 123:398–400
Velasquez MT, Kimmel PL, Michaelis OE (1990) Animal models of spontaneous diabetic kidney disease. FASEB J 4:2850–2859
Spontaneously Diabetic Rats: BHE Rat
Berdanier CD (1974) Metabolic abnormalities in BHE rats. Diabetologia 10:691–695
Durand AMA, Fisher M, Adams M (1964) Histology in rats as influenced by age and diet. Arch Pathol 77:268–277
Velasquez MT, Kimmel PL, Michaelis OE (1990) Animal models of spontaneous diabetic kidney disease. FASEB J 4:2850–2859
Spontaneously Diabetic Rats: LEW.1AR1/Ztm-iddm Rat
Jörns A, Kubat B, Tiedge M, Wedekind D, Hedrich HJ, Klöppel G, Lenzen S (2004) Pathology of the pancreas and other organs in the diabetic LEW.1AR1/Ztm-iddm rat, a new model of spontaneous insulin-dependent diabetes mellitus. Virchows Arch 444:183–189
Lenzen S, Tiedge M, Elsner M, Lortz S, Weiss H, Jörns A, Koppel G, Wedekínd D, Prokop SM, Hedrich HJ (2001) The LEW.1AR1/Ztm-iddm rat: a new model of spontaneous insulin-dependent diabetes mellitus. Diabetologia 44:1189–1196
Spontaneously Diabetic Mice: KK Mouse
Fujiwara T, Yoshioka S, Yoshioka T, Ushiyama I, Horikoshi H (1988) Characterization of new oral antidiabetic agent CS-045. Studies in KK and ob/ob mice and Zucker fatty rats. Diabetes 37:1549–1558
Herberg L, Coleman DL (1977) Laboratory animals exhibiting obesity and diabetes syndromes. Metabolism 26:59–99
Kondo K, Nozawa K, Tomida T, Ezaki K (1957) Inbred strains resulting from Japanese mice. Bull Exp Anim 6:107–112
Nakamura M (1962) A diabetic strain of the mouse. Proc Jpn Acad 38:348–352
Nakamura M, Yamada K (1967) Studies on a diabetic (KK) strain of the mouse. Diabetologia 3:212–221
Spontaneously Diabetic Mice: KK-Ay Mouse
Diani AR, Sawada GA, Zhang NY, Wyse BM, Connell CL, Vidmar TJ, Connell MA (1987) The KKAy mouse: a model for the rapid development of glomerular capillary basement membrane thickening. Blood Vessels 24:297–303
Hofmann CA, Edwards CW, Hillman RM, Colca JR (1992) Treatment of insulin-resistant mice with the oral antidiabetic agent pioglitazone: evaluation of liver GLUT2 and phosphoenolpyruvate carboxykinase expression. Endocrinology 130:735–740
Iwatsuka H, Shino A, Suzouki Z (1970) General survey of diabetic features of yellow KK mice. Endocrinol Jpn 17:23–35
Müller G, Satoh Y, Geisen K (1995) Extrapancreatic effects of sulfonylureas-a comparison between glimepiride and conventional sulfonylureas. Diabetes Res Clin Pract 28:S115–137
Shafrir E (1992) Animal models of non-insulin-dependent diabetes. Diabetes/Metab Rev 8:179–208
Sohda T, Momose Y, Meguro K, Kawamatsu Y, Sugiyama Y, Ikeda H (1990) Studies on antidiabetic agents. Synthesis and hypoglycemic activity of 5-[4-(pyridylalkoxy)benzyl]-2,4-thiazolidinediones. Arzneim Forsch/Drug Res 40:37–42
Takada Y, Takata Y, Iwanishi M, Imamura T, Sawa T, Morioka H, Ishihara H, Ishiki M et al. (1996) Effect of glimepiride (HOE490) on insulin receptors of skeletal muscles from genetically diabetic KK-Ay mouse. Eur J Pharmacol 308:205–210
Spontaneously Diabetic Mice: NOD Mouse
Baeder WL, Sredy J, Sehgal SN, Chang JY, Adams LM (1992) Rapamycin prevents the onset of insulin dependent diabetes mellitus (IDDM) in NOD mice. Clin Exp Immunol 89:174–178
Bergerot I, Ploix C, Petersen J, Moulin V, Rask C, Fabien N, Lindblad M, Mayer A, Czerkinsky C, Holmgren J, Thivolet C (1997) A cholera toxoid-insulin conjugate as an oral vaccine against spontaneous autoimmune diabetes. Proc Natl Acad Sci U S A 94:4610–4614
Charlton B, Bacelj A, Mandel TE (1988) Administration of silica particles or anti-Lyt2 antibody prevents β-cell destruction in NOD mice given cyclophosphamide. Diabetes 37:930–935
Elias D, Markovits D, Reshef T, van der Zee R, Cohen IR (1990) Induction and therapy of autoimmune diabetes in the nonobese diabetic (NOD/Lt) mouse by a 65-kDa heat shock protein. Proc Natl Acad Sci U S A 87:1576–1580
Geisen K, Deutschländer H, Gorbach S, Klenke C, Zimmermann U (1990) Function of barium alginate-microencapsulated xenogenic islets in different diabetic mouse models. In: Shafrir E (ed) Frontiers in diabetes research. Lessons from animal diabetes III. John Libby, London, pp 142–148
Hutchings PR, Cooke A (1995) Comparative study of the protective affect afforded by intravenous administration of bovine or ovine insulin to young NOD mice. Diabetes 44:906–910
Lee KU, Amano K, Yoon JW (1988) Evidence for initial involvement of macrophage in development of insulitis in NOD mice. Diabetes 37:989–991
Matsuba H, Jitsukawa T, Yamagata N, Uchida S, Watanabe H (1994) Establishment of rat glutamic acid decarboxylase (GAD)-reactive T-cell clones from NOD mice. Immunol Lett 42:101–103
Nicoletti F, Di Marco R, Barcellini W, Magro G, Schorlemmer HU, Kurrle R, Lunetta M, Grasso S, Zaccone P, Meroni PL (1994) Protection from experimental autoimmune diabetes in the non-obese diabetic mouse with soluble interleukin-1 receptor. Eur J Immunol 24:1843–1847
Serreze DV, Leiter EH (1994) Genetic and pathogenetic basis of autoimmune diabetes in NOD mice. Curr Opin Immunol 6:900–906
Tochino Y (1984) Breeding and characteristics of a spontaneously diabetic non obese strain (NOD mouse) of mice. In: Shafrir E, Renold AE (eds) Lessons from animal diabetes. John Libbey, London, pp 93–98
Velasquez MT, Kimmel PL, Michaelis OE (1990) Animal models of spontaneous diabetic kidney disease. FASEB J 4:2850–2859
Verdaguer J, Schmidt D, Amrani A, Anderson B, Averill N, Santamaria P (1997) Spontaneous autoimmune diabetes in monoclonal T cell nonobese diabetic mice. J Exp Med 186:1663–1676
Spontaneously Diabetic Mice: Obese Hyperglycemic Mice
Bleisch VR, Mayer J, Dickie MM (1952) Familial diabetes mellitus in mice associated with insulin resistance, obesity and hyperplasia of the islands of Langerhans. Am J Pathol 28:369–385
Coleman DL, Hummel KP (1973) The influence of genetic background on the expression of obese (ob) gene in the mouse. Diabetologia 9:287–293
Dickie MM (1962) New mutations. Mouse News Lett 27:37
Gill AM, Yen TT (1991) Effects of ciglitazone on endogenous plasma islet amyloid polypeptide and insulin sensitivity in obese-diabetic viable yellow mice. Life Sci 48:703–710
Halaas JL, Gajiwala KS, Maffei M, Cohen SL, Chait BT, Rabinowitz D, Lallone RL, Burley SK, Friedman JM (1995) Weight-reducing effects of the plasma protein encoded by the obese gene. Science 269:543–546
Hellman B (1967) Some metabolic aspects of the obesehyperglycemic syndrome in mice. Diabetologia 3:222–229
Herberg L, Coleman DL (1977) Laboratory animals exhibiting obesity and diabetes syndromes. Metabolism 26:59–99
Ingalls AM, Dickie MM, Snell GT (1950) Obese, a new mutation in the house mouse. J Hered 14:317–318
Mayer J, Bates MW, Dickie MM (1951) Hereditary diabetes in genetically obese mice. Science 113:746–747
Sirek A (1968) Spontaneous hereditary diabetes in laboratory animals. In: Pfeiffer EF (ed) Handbook of diabetes mellitus. Pathophysiology and clinical considerations, vol I. Lehmanns Verlag, München, pp 715–726
Stauffacher W, Lambert AE, Vecchio D, Renold AE (1967) Measurement of insulin activities in pancreas and serum of mice with spontaneous (“obese” and “New Zealand obese”) and induced (gold thioglucose) obesity and hyperglycemia, with considerations on the pathogenesis of the spontaneous syndrome. Diabetologia 3:230–237
Stein JM, Bewsher PD, Stowers JN (1970) The metabolism of ketones, triglyceride and monoglyceride in livers of obese hyperglycaemic mice. Diabetologia 6:570–574
Westman S (1968) Development of the obese-hyperglycaemic syndrome in mice. Diabetologia 4:141–149
Zhang Y, Proenca R, Maffei M, Barone M, Leopold L, Friedman JF (1994) Positional cloning of the mouse obese gene and its human homologue. Nature 372:425–432
Spontaneously Diabetic Mice: Diabetic db/db Mice
Berglund O, Frankel BJ, Hellman B (1980) Development of the insulin secretory defect in genetically diabetic (db/db) mouse. Acta Endocrinol 87:543–551
Chen H, Charlat O, Tartaglia LA, Woolf EA, Weng X, Ellis SJ, Lakey ND, Culpepper J, Moore KJ, Breitbart RE, Duyk GM, Tepper RI, Morgenstern JP (1996) Evidence that the diabetes gene encodes the leptin receptor. Identification of a mutation in the leptin receptor gene in db/db mice. Cell 84:491–495
Coleman DL, Hummel KP (1967) Studies with the mutation diabetes in the mouse. Diabetologia 3:238–248
Coleman DL, Hummel KP (1969) Effects of parabiosis of normal with genetically diabetic mice. Am J Physiol 217:1298–1304
Friedman JF, Halaas JL (1998) Leptin and the regulation of body weight in mammals. Nature 395:763–770
Gardner K (1978) Glomerular hyperfiltration during the onset of diabetes mellitus in two strains of diabetic mice (C57BL/6J db/db and C57BL/KsJ db/db). Diabetologia 15:59–63
Herberg L, Coleman DL (1977) Laboratory animals exhibiting obesity and diabetes syndromes. Metabolism 26:59–99
Hummel KP, Dickie MM, Colemann DL (1966) Diabetes, a new mutation in the mouse. Science 153:1127–1128
Lee SM (1982) The effect of chronic α-glycosidase inhibition on diabetic nephropathy in the db/db mouse. Diabetes 13:249–254
Lee GH, Proenca R, Montez JM, Carroll KM, Darvishzadeh JG, Li JI, Friedman JM (1996) Abnormal splicing in the leptin receptor in diabetic mice. Nature 379:632–635
Leiter EH, Coleman DL, Ingram DK, Reynold MA (1983) Influence of dietary carbohydrate on the induction of diabetes in C5BL/KsJ-db/db diabetes mice. J Nutr 113:184–195
Li C, Ioffe E, Fidahusein N, Connolly E, Friedman JM (1998) Absence of soluble leptin receptor in plasma from dbPas/dbPas and other db/db mice. J Biol Chem 273:10078–10082
Like AA, Lavine RL, Poffenbarger PL, Chick WI (1972) Studies on the diabetic mutant mouse. VI Evolution of glomerular lesions and associated proteinuria. Am J Pathol 66:193–224
Raizada MK, Tan G, Fellows RE (1980) Fibroblastic cultures from the diabetic db/db mouse. Demonstration of decreased insulin receptors and impaired responses to insulin. J Biol Chem 255:9149–9155
Stearns SB, Benz CA (1978) Glucagon and insulin relationships in genetically diabetic (db/db) and streptozotocin-induced diabetic mice. Horm Metab Res 10:20–33
Tartaglia LA, Dembski M, Wenig X, Deng N, Culpepper J, Devos R, Richards GJ, Campfield LA, Clark FT, Deeds J (1995) Identification and expression cloning of a leptin receptor, OB-R. Cell 83:1263–1271
Spontaneously Diabetic Mice: Diabetes Obesity Syndrome in CBA/Ca Mice
Campbell IL, Das AK (1982) A spontaneous diabetic syndrome in the CBA/Ca laboratory mouse. Biochem Soc Trans 10:392
Connelly DM, Taberner PV (1985) Insulin independent diabetes in male mice from an inbred CBA strain. Endocrinology 104(Suppl):139
Connelly DM, Taberner PV (1989) Characterization of spontaneous diabetes obesity syndrome in mature CBA/Ca mice. Pharmacol Biochem Behav 34:255–259
Sclafani A (1984) Animal models in obesity: classification and characterization. Int J Obes 8:491–508
Spontaneously Diabetic Mice: Wellesley Mouse
Cahill GF, Jones EE, Lauris V, Steinke J, Soeldner JS (1967) Studies on experimental diabetes in the Wellesley hybrid mouse. II Serum insulin levels and response of peripheral tissues. Diabetologia 3:171–174
Gleason RE, Lauris V, Soeldner JS (1967) Studies on experimental diabetes in the Wellesley hybrid mouse. III Dietary effects and similar changes in a commercial Swiss-Hauschke strain. Diabetologia 3:175–178
Jones E (1964) Spontaneous hyperplasia of the pancreatic islets associated with glycosuria in hybrid mice. In: Brolin SE, Hellman B, Knutson H (eds) The structure and metabolism of pancreatic islets. Pergamon Press, Oxford, pp 189–191
Like AA, Jones EE (1967) Studies on experimental diabetes in the Wellesley hybrid mouse. IV. Morphologic changes in islet tissue. Diabetologia 3:179–187
Chinese Hamster
Butler L (1967) The inheritance of diabetes in the Chinese hamster. Diabetologia 3:124–129
Frenkel BJ, Gerich JE, Hagura R, Fanska RE, Gerritsen GC, Grodsky GM (1974) Abnormal secretion of insulin and glucagon by the in vitro perfused pancreas of the genetically diabetic Chinese hamster. J Clin Invest 53:1637–1646
Gerritsen GC (1982) The Chinese hamster as a model for the study of diabetes mellitus. Diabetes 31(Suppl 1):14–23
Gerritsen GC, Dulin WE (1967) Characterization of diabetes in the Chinese hamster. Diabetologia 3:74–78
Gundersen K, Yerganian G, Lin BJ, Gagnon H, Bell F, McRae W, Onsberg T (1967) Diabetes in the Chinese hamster. Some clinical and metabolic aspects. Diabetologia 3:85–91
Luse SA, Caramia F, Gerritsen G, Dulin WE (1967) Spontaneous diabetes mellitus in the Chinese hamster: an electron microscopic study of the islets of Langerhans. Diabetologia 3:97–108
Malaisse W, Malaisse-Lagae F, Gerritsen GC, Dulin WE, Wright PH (1967) Insulin secretion in vitro by the pancreas of the Chinese hamster. Diabetologia 3:109–114
Meier H, Yerganian GA (1959) Spontaneous hereditary diabetes mellitus in Chinese hamster (Cricetulus griseus). I. Pathological findings. Proc Soc Exp Biol Med 100:810–815
Meier H, Yerganian G (1961a) Spontaneous diabetes mellitus in the Chinese hamster (Cricetulus griseus). II Findings in the offspring of diabetic parents. Diabetes 10:12–18
Meier H, Yerganian G (1961b) Spontaneous hereditary diabetes mellitus in the Chinese hamster (Cricetulus griseus). III Maintenance of a diabetic hamster colony with the aid of hypoglycemic therapy. Diabetes 10:19–21
Shirai T, Welsh GW, Sims EAH (1967) Diabetes mellitus in the Chinese hamster. II The evolution of renal glomerulopathy. Diabetologia 3:266–286
Sims EAH, Landau BR (1967) Diabetes mellitus in the Chinese hamster. I Metabolic and morphologic studies. Diabetologia 3:115–123
Sirek A (1968) Spontaneous hereditary diabetes in laboratory animals. In: Pfeiffer EF (ed) Handbook of diabetes mellitus. Pathophysiology and clinical considerations, vol I. Lehmanns Verlag, München, pp 715–726
Sirek OV, Sirek A (1967) The colony of Chinese hamsters of the C.H. Best institute. A review of experimental work. Diabetologia 3:65–73
Soret MG, Dulin WE, Matthew’s J, Gerritsen GC (1974) Morphologic abnormalities observed in retina, pancreas and kidney of diabetic Chinese hamsters. Diabetologia 10:567–579
Other Species with Inherited Diabetic Symptoms: SAND Rat
Brodoff BN, Penhos JC, Levine R, White R (1967) The effect of feeding and various hormones on the glucose tolerance of the sand rat (Psammomys obesus). Diabetologia 3:167–170
DeFronzo R, Miki E, Steinke J (1967) Diabetic syndrome in sand rats. Diabetologia 3:140–142
Dubault J, Boulanger M, Espinal J, Marquie G, Petkov P, du Boistesselin R (1995) Latent autoimmune diabetes mellitus in adult humans with non-insulin-dependent diabetes: is Psammomys obesus a suitable animal model? Acta Diabetol 32:92–94
Hackel BB, Frohman LA, Mikat E, Lebovitz HE, Schmidt-Nielsen K (1965a) Review of current studies on the effect of diet on the glucose tolerance of the sand rat (Psammomys obesus). Ann N Y Acad Sci 131:459–463
Hackel DB, Schmidt-Nielson K, Haines HB, Miai E (1965b) Diabetes mellitus in the sand rat (Psammomys obesus) – pathologic studies. Lab Invest 14:200–207
Hackel DB, Mikat E, Lebovitz HE, Schmidt-Nielsen K, Horton ES, Kinney TD (1967) The sand rat (Psammomys obesus) as an experimental animal in studies of diabetes mellitus. Diabetologia 3:130–134
Haines H, Hackel DB, Schmidt-Nielsen K (1965) Experimental diabetes mellitus induced by diet in the sand rat. Am J Physiol 208:297–300
Kalderon B, Gutman A, Levy E, Shafrir E, Adler JH (1986) Characterization of stages in the development of obesity diabetes syndrome in the sand rat (Psammomys obesus). Diabetes 35:717–724
Marquie G, Duhault J, Jacotot B (1984) Diabetes mellitus in sand rats (Psammomys obesus). Metabolic pattern during development of the diabetic syndrome. Diabetes 33:438–443
Miki E, Like AA, Steinke J, Soeldner JS (1967) Diabetic syndrome in sand rats. Diabetologia 3:135–139
Schmidt-Nielsen K, Haines HB, Hackel DB (1964) Diabetes mellitus in the sand rat induced by standard laboratory diets. Science 143:689–690
Shafrir E (1992) Animal models of non-insulin-dependent diabetes. Diabetes/Metab Rev 8:179–208
Strasser H (1968) A breeding program for spontaneously diabetic experimental animals: Psammomys obesus (sand rat) and Acomys cahirinus (spiny mouse). Lab Anim Care 18:328–338
Other Species with Inherited Diabetic Symptoms: Spiny Mouse
Brunk R (1971) Spontandiabetes bei einer weiteren Stachelmausform (Acomys c. cahirinus Desmarest, 1819) Z Versuchstierk 13:81–86
Gonet AE, Stauffacher W, Pictet R, Renold AE (1965) Obesity and diabetes mellitus with striking congenital hyperplasia of the islets of Langerhans in spiny mice (Acomys cahirinus). I Histological findings and preliminary metabolic observations. Diabetologia 1:162–171
Junod A, Letarte J, Lambert AE, Stauffacher W (1969) Studies in spiny mice (Acomys cahirinus): metabolic state and pancreatic insulin release in vitro. Horm Metab Res 1:45–52
Pictet R, Orci L, Gonet AE, Rouiller C, Renold AE (1967) Ultrastructural studies of the hyperplastic islets of Langerhans of spiny mice (Acomys cahirinus) before and during the development of hyperglycemia. Diabetologia 3:188–211
Renold AE, Dulin WE (1967) Spontaneous diabetes in laboratory animals. Diabetologia 3:63–64
Shafrir E, Teitelbaum A, Cohen AM (1972) Hyperlipidemia and impaired glucose tolerance in Acomys cahirinus maintained on synthetic carbohydrate diets. Isr J Med Sci 8:990–992
Other Species with Inherited Diabetic Symptoms: African Hamster (Mystromys albicaudatus)
Packer JT, Kraner KL, Rose SD, Stuhlman A, Nelson RL (1970) Diabetes mellitus in Mystromys albicaudatus. Arch Pathol 89:410–415
Schmidt G, Martin AP, Stuhlman RA, Townsend JF, Lucas FV, Vorbeck ML (1974) Evaluation of hepatic mitochondrial function in the spontaneously diabetic Mystromys albicaudatus. Lab Invest 30:451–457
Stuhlman RA, Packer JT, Doyle RE (1972) Spontaneous diabetes mellitus in Mystromys albicaudatus. Repeated glucose values from 620 animals. Diabetes 21:715–721
Stuhlman RA, Srivastava PK, Schmidt G, Vorbeck ML, Townsend JF (1974) Characterization of diabetes mellitus in South African Hamsters (Mystromys albicaudatus). Diabetologia 10:685–690
Stuhlman RA, Packer JT, Doyle RE, Brown RV, Townsend JF (1975) Relationship between pancreatic lesions and serum glucose values in Mystromys albicaudatus. Lab Anim Sci 25:168–174
Other Species with Inherited Diabetic Symptoms: Tuco-Tuco
Velasquez MT, Kimmel PL, Michaelis OE (1990) Animal models of spontaneous diabetic kidney disease. FASEB J 4:2850–2859
Wise PH, Weir BJ, Hime JM, Forrest E (1972) The diabetic syndrome in the Tuco-Tuco (Ctenomis talarum). Diabetologia 8:165–172
Other Species with Inherited Diabetic Symptoms: Macaca Nigra
Howard CF Jr (1972) Spontaneous diabetes in Macaca nigra. Diabetes 21:1077–1090
Howard CF Jr (1974a) Diabetes in Macaca nigra: metabolic and histologic changes. Diabetologia 10:671–677
Howard CF Jr (1974b) Correlations of serum triglyceride and pre-beta lipoprotein levels to the severity of spontaneous diabetes in Macaca nigra. J Clin Endocrinol Metab 38:856–860
Howard CF Jr (1975) Basement membrane thickness in muscle capillaries of normal and spontaneously diabetic Macaca nigra. Diabetes 24:201–206
Adipose Tissue-Specific Transgenic Mouse Models
Agelion LB, Walsh A, Hayek T, Moulin P, Jiang XC, Shelanski SA, Breslow JL, Tall AR (1991) Reduced high density lipoprotein cholesterol in human cholesteryl ester transfer protein transgenic mice. J Biol Chem 266:10796–10800
Ahima RS (2006) Adipose tissue as an endocrine organ. Obesity 14(Suppl 5):242S–249S
Arai T, Yamashita S, Hirano K, Sakai N, Kotami K, Fujioka S, Nozaki S, Keno Y, Yamane M, Shinohara E (1994) Increased plasma cholesteryl ester transfer protein in obese subjects. A possible mechanism for the reduction of serum HDL cholesterol levels in obesity. Arterioscler Thromb 14:1129–1136
Barlow C, Schroeder M, Lekstrom-Hines J, Kylefjord H, Deng CX, Wynshaw-Boris A, Spiegelman BM, Xanthopoulos KG (1997) Targeted expression of Cre recombinase to adipose tissue of transgenic mice directs adipose-specific excision of loxP-flanked gene segments. Nucleic Acids Res 25:2543–2545
Bealnger C, Luu-The V, Dupont P, Tchernof A (2002) Adipose tissue intracrinology: potential importance of local androgen/estrogen metabolism in the regulation of adiposity. Horm Metab Res 34:737–745
Chen HC, Farese RV Jr (2002) Determination of adipocyte size by computer image analysis. J Lipid Res 43:986–989
Dullaart RP, Sluiter WJ, Dikkeschei LD, Hoogenberg K, Van Tol A (1994) Effect of adiposity on plasma lipid transfer protein activities: a possible link between insulin resistance and high density lipoprotein metabolism. Eur J Clin Invest 24:188–194
Farley FW, Soriano P, Steffen LS, Dymecki SM (2000) Widespread recombinase expression using FLPeR (flipper) mice. Genesis 28:106–110
Flier JS (2004) Obesity wars: molecular progress confronts an expanding epidemic. Cell 116:337–350
Fu Y, Luo N, Lopes-Virella MF, Garvey WT (2002) The adipocyte lipid binding protein (ALBP/ap2) gene facilitates foam cell formation in human THP-1 macrophages. Atherosclerosis 165:259–269
Horton JD, Shimomura I, Ikemoto S, Bashmakov Y, Hammer RE (2003) Overexpression of sterol regulatory element-binding protein-1a in mouse adipose tissue produces adipocyte hypertrophy, increased fatty acid secretion, and fatty liver. J Biol Chem 278:36652–36660
Jiang XC, Agellon LB, Walsh A, Breslow JP, Tall (1992) Dietary cholesterol increases transcription of the human cholesteryl ester transfer protein gene in transgenic mice. Dependence on natural flanking sequences. J Clin Invest 90:1290–1295
Jiang XC, Moulin P, Quinet E, Goldberg IJ, Yacoub LK, Agellon LB, Compton D, Schnitzer-Polokoff R, Tall AR (1991) Mammalian adipose tissue and muscle are major sources of lipid transfer protein mRNA. J Biol Chem 247:4631–4639
Jones JR, Shelton KD, Magnuson MA (2005) Strategies for the use of site-specific recombinases in genome engineering. Methods Mol Med 103:245–257
Jurczak MJ, Danos AM, Rehrmann VR, Allison MB, Greenberg CC, Brady MJ (2007) Transgenic overexpression of protein targeting to glycogen markedly increases adipocyte glycogen storage in mice. Am J Physiol Endocrinol Metab 292:E952–E963
Kopecky J, Clarke G, Enerback S, Spiegelman B, Kozak LP (1995) Expression of the mitochondrial uncoupling protein gene from the aP2 gene promoter prevents genetic obesity. J Clin Invest 96:2914–2923
Laustsen PG, Michael MD, Crute BE, Cohen SE, Ueki K, Kulkarni RN, Keller SR, Lienhard GE, Kahn CR (2002) Lipoatrophic diabetes in Irs1(−/−)/Irs3(−/−) double knockout mice Genes Dev 16:3213–3222
Le Lay S, Ferre P, Dugail I (2004) Adipocyte cholesterol balance in obesity. Biochem Soc Transact 32:103–106
Morton NM, Paterson JM, Masuzaki H et al (2004) Novel adipose tissue-mediated resistance to diet-induced visceral obesity in 11 beta-hydroxysteroid dehydrogenase type 1-deficient mice. Diabetes 53:931–938
Quinet EM, Huerta P, Nancoo D, Tall AR, Marcel YL, McPherson R (1993) Adipose tissue cholesteryl ester transfer protein mRNA in response to probucol treatment: cholesterol and species dependence. J Lipid Res 34:845–852
Quinet EM, Tall AR, Ramakrishnan R, Rudel L (1991) Plasma lipid transfer protein as a determinant of the atherogenicity of monkey plasma lipoproteins. J Clin Invest 87:1559–1566
Radeau T, Lau P, Robb M, McDonnell M, Ailhaud G, McPherson R (1995) Cholesteryl ester transfer protein (CETP) mRNA abundance in human adipose tissue: relationship to cell size and membrane cholesterol content. J Lipid Res 36:2552–2561
Remillard P, Shen G, Milne R, Maheux P (2001) Induction of cholesteryl ester transfer protein in adipose tissue and plasma of the fructore-fed hamster. Life Sci 69:677–687
Sauer B (1998) Inducible gene targeting in mice using the Cre/lox system. Methods 14:381–392
Shen GX, Angel A (1995) Regulation of cholesteryl ester transfer protein in adipose tissue: comparison between hamster and rat species. Am J Physiol 269:99–107
Shepherd PR, Gnudi L, Tozzo E, Yang H, Leach F, Kahn BB (1993) Adipose cell hyperplasia and enhanced glucose disposal in transgenic mice overexpressing GLUT4 selectively in adipose tissue. J Biol Chem 268:22243–22246
Skurk T, Hauner H (2004) Obesity and impaired fibrinolysis: role of adipose production of plasminogen activator inhibitor-1. Int J Obes Relat Metab Disord 28:1357–1364
Tall AR (1993) Plasma cholesteryl ester transfer protein. J Lipid Res 120:1255–1274
Weisberg SP, McCann D, Desai M, Rosenbaum M, Leibel RL, Ferrante AW (2003) Obesity is associated with macrophage accumulation in adipose tissue. J Clin Invest 112:1796–1808
Xu H, Barnes GT, Yang Q et al (2003) Chronic inflammation in fat plays a crucial role in the development of obesity-related insulin resistance. J Clin Invest 112:1821–1830
Yvan-Charvet L, Even P, Bloch-Faure M, Guerre-Millo M, Moustaid-Moussa N, Ferre P, Quignard-Boulange A (2005) Deletion of the angiotensin type 2 receptor (AT2R) reduces adipose cell size and protects from diet-induced obesity and insulin resistance. Diabetes 54:991–999
Zhou H, Li Z, Hojjati MR, Jang D, Beyer TP, Cao G, Tall AR, Jiang XC (2006) Adipose tissue-specific CETP expression in mice: impact on plasma lipoprotein metabolism. J Lipid Res 47:2011–2019
Metabolic Systems Biology
Abe H, Yamada N, Kamata K, Kuwaki T, Shimada M, Osuga J, Shionoiri F, Yahagi N, Kadowaki T, Tamemoto H, Ishibashi S, Yazaki Y, Makuuchi M (1998) Hypertension, hypertriglyceridemia, and impaired endothelium-dependent vascular relaxation in mice lacking insulin receptor substrate-1. J Clin Invest 101:1784–1788
Accili D, Drago J, Lee EJ, Johnson MD, Cool MH, Salvatore P, Asico LD, Jose PA, Taylor SI, Westphal H (1996) Early neonatal death in mice homozygous for a null allele of the insulin receptor gene. Nat Genet 12:106–109
Aichele P, Hyburtz D, Ohashi POS, Odermatt B, Zinkernagel RM, Hengartner H, Pircher H (1994) Peptide-induced T-cell tolerance to prevent autoimmune diabetes in a transgenic mouse model. Proc Natl Acad Sci U S A 91:444–448
Aizawa T, Asanuma N, Terauchi Y, Suzuki N, Komatsu M, Itoh N, Nakabayashi T, Hidaka H, Ohnota H, Yamauchi K, Yasuda K, Yazaki Y, Kodawaki T, Hashizume K (1996) Analysis of the pancreatic β-cell in the mouse with targeted disruption of the pancreatic β-cell-specific glucokinase gene. Biochem Biophys Res Commun 229:460–465
Almind K, Kulkarni RN, Lannon SM, Kahn CR (2003) Identification of interactive loci linked to insulin and leptin in mice with genetic insulin resistance. Diabetes 52:1535–1543
Araki E, Lipes MA, Patti ME, Brüning JC, Haag B, Johnson RS, Kahn CR (1994) Alternative pathway of insulin signalling in mice with targeted disruption of the IRS-1 gene. Nature 372:128–129
Argmann CA, Chambon P, Auwerx J (2005) Mouse phenogenomics: the fast track to “systems metabolism”. Cell Metab 2:349–360
Barak Y, Nelson MC, Ong ES, Jones YZ, Ruiz-Lozano P, Chien KR, Koder A, Evans RM (1999) PPARγ is required for placental, cardia and adipose tissue development. Mol Cell 4:585–595
Bickel PE (2004) Metabolic fuel selection: the importance of being flexible. J Clin Invest 114:1547–1549
Birk OS, Douek DC, Elias D, Takacs K, Dewchand H, Gur SL, Walker MD, Van der Zee R, Cohen IR, Altman DM (1996) A role Hsp60 in autoimmune diabetes: analysis of a transgenic model. Proc Natl Acad Sci U S A 93:1032–1037
Bluher M, Kahn BB, Kahn CR (2003) Extended longevity in mice lacking the insulin receptor in adipose tissue. Science 299:572–574
Branda C, Dymecki S (2004) Talking about a revolution: the impact of site-specific recombinases on genetic analyses in mice. Dev Cell 6:7–28
Brünning JC, Gautam D, Burks DJ, Gillette J, Schubert M, Orban PC, Klein R, Krone W, Müller-Wieland D, Kahn CR (2000) Role of brain insulin receptor incontrol of body weight and reproduction. Science 289:2122–2125
Brüning JC, Michael MD, Winnay JN, Hayashi T, Horsch D, Accili D, Goodyear LJ, Kahn CR (1998) A muscle-specific insulin receptor knockout exhibits features of the metabolic syndrome of NIDDM without altering glucose tolerance. Mol Cell 2:559–569
Brüning JC, Winnay J, Bonner-Weir S, Taylor SI, Accili D, Kahm CR (1997) Development of a novel polygenic model of NIDDM in mice heterozygous for IR and IRS-1 null alleles. Cell 88:561–572
Djoudi F, Weinheimer CJ, Saffitz JE, Pitchford C, Bastin J, Gonzalez FJ, Kelly DP (1998) A gender-related defect in lipid metabolism and glucose transport and glucose homeostasis in peroxisome proliferator-activated receptor α-deficient mice. J Clin Invest 102:1083–1091
Fernandez AM, Kim JK, Yakar S, Dupont J, Hernandez-Sanchez C, Castle AL, Filmore J, Shulman GI, Le Roith D (2001) Functional inactivation of the IGF-1 and insulin receptors in skeletal muscle causes type 2 diabetes. Genes Dev 15:1926–1934
He W, Barak Y, Hevener A, Olson P, Liao D, Le J, Nelson M, Ong E, Olefsky JM, Evans RM (2003) Adipose-specific peroxisome-activated receptor γ knockout causes insulin resistance in fat and liver but not in muscle. Proc Natl Acad Sci U S A 100:15712–15717
Jenkins AB, Storlien LH (1997) Insulin resistance and hyperinsulinaemia in insulin receptor substrate-1 knockout mice. Diabetologia 40:1113–1114
Joshi RL, Lamothe B, Cordonnier N, Mesbah K, Monthioux E, Jami J, Bucchini D (1996) Targeted disruption of the insulin receptor gene in the mouse results in neonatal lethality. EMBO J 15:1542–1547
Katz EB, Stenbit AE, Hatton K, DePinho R, Charron MJ (1995) Cardiac and adipose tissue abnormalities but not diabetes in mice deficient in GLUT4. Nature 377:151–155
Kim JK, Zisman A, Fillmore JJ, Peroni OD, Kotani K, Perret P, Zong H, Dong J, Kahn CR, Kahn BB, Shulamn GI (2001) Glucose toxicity and the development of diabetes in mice with muscle-specific inactivation of GLUT4. J Clin Invest 108:153–160
Kulkarni RN, Brüning JC, Winnay JN, Postic C, Magnuson MA, Kahn RC (1999) Tissue specific knockout of the insulin receptor in pancreatic β cells creates an insulin secretory defect similar to that in type 2 diabetes. Cell 96:329–339
Kulkarni RN, Holzenberger M, Shih DQ, Ozcan U, Stoffel M, Magnuson MA, Kahn CR (2002) β-cell-specific deletion of the Igf1 receptor leads to hyperinsulinemia and glucose intolerance but does not alter β-cell mass. Nat Genet 31:111–115
Lauro D, Kido Y, Castle AL, Zarnowski MJ, Hayashi H, Ebina Y, Accili D (1998) Impaired glucose tolerance in mice with a targeted impairment of insulin action in muscle and adipose tissue. Nat Genet 20:294–298
Laustsen PG, Michael MD, Crute BE, Cohen SE, Ueki K, Kulkarni RN, Keller SR, Lienhard GE, Kahn CR (1998) Lipoatrophic diabetes in Irs(−/−)Irs(−/−) double knockout mice. Genes Dev 16:3213–3222
Lavan BE, Lane WS, Lienhard GE (1997) The 60-kDa phosphotyrosine protein in insulin-treated adipocytes ia a new member of the insulin receptor substrate family. J Biol Chem 272:11439–11443
Metzger D, Chambon P (2001) Site- and time-specific gene targeting in the mouse. Methods 24:71–80
Michael MD, Kulkarni RN, Postic C, Previs SF, Shulman GI, Magnuson MA, Kahn CR (2000) Loss of insulin signaling in hepatocytes leads to severe insulin resistance and progressive hepatic dysfunction. Mol Cell 6:87–97
Moller DE (1994) Transgenic approaches to the pathogenesis of NIDDM. Diabetes 43:1394–1401
Moritani M, Yoshimoto K, Ii S, Kondo M, Iwahana H, Yamaoka T, Sano T, Nakano N, Kikutani H, Itakura M (1996) Prevention of adoptively transferred diabetes in nonobese diabetic mice with IL-10-transduced islet-specific Th1 lymphocytes: a gene therapy model of autoimmune diabetes. J Clin Invest 98:1851–1859
Muoio DM, MacLean PS, Lang DB, Li S, Houmard JA, Way JM, Winegar DA, Corton JC, Dohm GL, Kraus WE (2002) Fatty acid homeostasis and induction of lipid regulatory genes in skeletal muscles of peroxisome proliferator-activated receptor (PPAR) α knock-out mice. Evidence for compensatory regulation by PPARδ. J Biol Chem 277:26089–26097
Nandi A, Kitamura Y, Kahn CR, Accilli D (2004) Mouse models of insulin resistance. Physiol Rev 84:623–647
Ohashi PS, Oehen S, Buerki K, Pircher H, Ohashi CT, Odermatt B, Malissen B, Zinkernagel RM, Hengartner H (1991) Ablation of “tolerance” and induction of diabetes by virus infection in viral antigen transgenic mice. Cell 65:305–317
Oldstone MBA, Nerenberg M, Southern P, Price J, Lewicki H (1991) Virus infection triggers insulin-dependent diabetes mellitus in a transgenic model: role of anti-self (virus) immune response. Cell 65:319–331
Palmiter RD, Behringer RR, Quaife CJ, Maxwell F, Maxwell IH, Brinster RL (1987) Cell lineage ablation in transgenic mice by cell-specific expression of a toxin gene. Cell 50:435–443
Plum L, Wunderlich FT, Baudler S, Krone W, Brüning C (2005) Transgenic and knockout mice in diabetes research: novel insights into pathophysiology, limitations, and perspectives. J Physiol 20:152–161
Rangwala SM, Lazar MA (2004) Peroxisome proliferator-activated receptor γ in diabetes and metabolism. Trends Pharmacol Sci 25:331–336
Terauchi Y, Iwamoto K, Tamemoto H, Komeda K, Ishii C, Kanazawa Y, Asanuma N, Aizawa T, Akanuma Y, Yasuda K, Kodama T, Tobe K, Yazaki Y, Kadowaki T (1997) Development of non-insulin-dependent diabetes mellitus in the double knockout mice with disruption of insulin receptor substrate-1 and β-cell glucokinase genes. Genetic reconstruction of diabetes as a polygenic disease. J Clin Invest 99:861–866
Von Herrath MG, Holz A (1997) Pathological changes in the islet milieu precede infiltration of islets and destruction in β-cells by autoreactive lymphocytes in a transgenic model of virus-induced IDDM. J Autoimmun 10:231–238
Von Herrath MG, Dockter J, Oldstone MBA (1994) How virus induces a rapid or slow onset insulin-dependent diabetes mellitus in a transgenic mouse model. Immunity 1:231–242
Von Herrath MG, Guerder S, Lewicki H, Flavell RA, Oldstone MBA (1995) Coexpression of B7–1 and viral (“self”) transgenes in pancreatic β-cells can break peripheral ignorance and lead to spontaneous autoimmune diabetes. Immunity 3:727–738
Von Herrath MG, Hormann D, Gairin JE, Oldstone MBA (1997) Pathogenesis and treatment of virus-induced autoimmune diabetes: novel insights gained from the RIP-LCVM transgenic mouse model. Biochem Soc Trans 25:630–635
Withers DJ, Gutierrez JS, Towery H, Burks DJ, Ren J-M, Previs S, Zhang Y, Bernal D, Pons S, Shulman GI, Bonner-Weir S, White MF (1998) Disruption of IRS-2 caused type 2 diabetes. Nature 391:900–907
Zhang J, Fu M, Cui T, Xiong C, Xu K, Zhong W, Xiao Y, Floyd D, Liang J, Li E, Song Q, Chen YE (2004) Selective disruption of PPARγ2 impairs the development of adipose tissue and insulin sensitivity. Proc Natl Acad Sci U S A 101:10703–10708
Zisman A, Peroni OD, Abel ED, Michael MD, Mauvais-Jarvis F, Lowell BB, Wojtaszewski JF, Hirshman MF, Virkamaki A, Goodyear LJ, Kahn CR, Kahn BB (2000) Targeted disruption of the glucose transporter 4 selectivity in muscle causes insulin resistance and glucose intolerance. Nat Med 6:924–928
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Müller, G. (2015). Genetically Diabetic Animals. In: Hock, F. (eds) Drug Discovery and Evaluation: Pharmacological Assays. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-27728-3_64-1
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