Obesity/diabetes in mice with mutations in leptin or leptin receptor genes

Animal Models of Diabetes, Second Edition: Frontiers in Research

Volumn , Issue , 2007, Pages 61-102

  Chua, Streamson ^a   Herberg, Lieselotte ^b   Leiter, Edward H ^c  

^a ALBERT EINSTEIN COLLEGE OF MEDICINE   (United States)

^b HEINRICH HEINE UNIVERSITY   (Germany)

^c JACKSON LABORATORY   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

EID: 85014820196     PISSN: None     EISSN: None     Source Type: Book    
DOI: None     Document Type: Chapter

References (244)

1. Ahima RS, Flier JS. (2000) Leptin. Annu Rev Physiol 62:413-437.
2. Alon T, Friedman JM. (2006) Late-onset leanness in mice with targeted ablation of melanin concentrating hormone neurons. J Neurosci 26:389-397.
3. Amir S. (1981) Behavioral response of the genetically obese (ob/ob) mouse to heat stress: Effects of naloxone and prior exposure to immobilization stress. Physiol Behav 27:249-353.
4. Ashwell M, Meade CJ, Medawar P, Sowter C. (1977) Adipose tissue: Contributions of nature and nurture to the obesity of an obese mutant mouse (ob/ob). Proc R Soc Lond B 195:343-353.
5. Bado A, Levasseur S, Attoub S, et al. (1998) The stomach is a source of leptin. Nature 394:790-793.
6. Balthasar N, Coppari R, McMinn J, et al. (2004) Leptin receptor signaling in POMC neurons is required for normal body weight homeostasis. Neuron 42:983-991.
7. Bates SH, Kulkarni RN, Seifert M. Myers, MG. Jr. (2005) Roles for leptin receptor/STAT3- dependent and independent signals in the regulation of glucose homeostasis. Cell Metab 1:169-178.
8. Bates SH, Stearns WH, Dundon TA, et al. (2003) STAT3 signaling is required for leptin regulation of energy balance but not reproduction. Nature 421:856-859.
9. Batt RA. (1972) The response of the reproductive system in the female mutant mouse, obese (genotype ob/ob) to gonadotrophin-releasing hormones. J Reprod Fertil 31:496-497.
10. Batt RA, Everard DM, Gillies G, et al. (1982) Investigation into the hypogonadism of the obese mouse (genotype ob/ob). J Reprod Fertil 64:363-371.
11. Batt RA, Harrison GA. (1960) Features of the “adipose” mouse. Heredity 15:335-337.
12. Batt RA, Harrison GA. (1963) The reproductive system of the adipose mouse. J Heredity 54:135-138.
13. Begin-Heick N. (1996) Beta-adrenergic receptors and G-proteins in the ob/ob mouse. Int J Obesity 20: Suppl 3, S32-S35.
14. Bellward K, Dauncey MJ. (1988) Behavioral energy regulation in lean and genetically obese (ob/ob) mice. Physiol Behav 42:433-438.
15. Black MA, Begin-Heick N. (1995) Growth and maturation of primary-cultured adipocytes from lean and ob/ob mice. J Cell Biochem 58:455-463.
16. Bock T, Pakkenberg B, Buschard K. (2003) Increased islet volume but unchanged islet number in ob/ob mice. Diabetes 52:1716-1722.
17. Bock T, Pakkenberg B, Buschard K. (2005) Genetic background determines the size and structure of the endocrine pancreas. Diabetes 54:133.
18. Bohlen HG, Niggl BA. (1979) Arteriolar anatomical and functional abnormalities in juvenile mice with genetic or streptozotocin-induced diabetes mellitus. Circ Res 45:390-396.
19. Bohlen HG, Niggl BA. (1980) Early arteriolar disturbances following streptozotocin-induced diabetes mellitus in adult mice. Microvasc Res 20:19-29.
20. Boillot D, Assan R, Dardenne M, et al. (1986) T-lymphopenia and T-cell imbalance in diabetic db/db mice. Diabetes 35:198-203.
21. Bower G, Brown DM, Steffes MW, et al. (1980) Studies of the glomerular mesangium and the juxtaglomerular apparatus in the genetically diabetic mouse. Lab Invest 43:333-341.
22. Bray GA. (1991) Obesity, a disorder of nutrient partitioning: The MONA LISA hypothesis. J Nutr 121:1146-1162.
23. Bray GA, York DA. (1971) Genetically transmitted obesity in rodents. Physiol Rev 51:598-646.
24. Bray GA, York DA. (1979) Hypothalamic and genetic obesity in experimental animals: An autonomic and endocrine hypothesis. Physiol Rev 59:719-809.
25. Brown JA, Chua SC Jr, Liu SM, et al. (2000) Spontaneous mutation in the db gene results in obesity and diabetes in CD-1 outbred mice. Am J Physiol 278:R320-R330.
26. Burcelin R, Kamohara S, Li J, et al. (1999) Acute intravenous leptin infusion increases glucose turnover but not skeletal muscle glucose uptake in ob/ob mice. Diabetes 48:1264-1269.
27. Busso N, So A, Chobaz-Peclat V, et al. (2002) Leptin signaling deficiency impairs humoral and cellular immune responses and attenuates experimental arthritis. J Immunol 168:875-882.
28. Calcagnetti DJ, Flynn JJ, Margules DL. (1987) Opioid-induced linear running in obese (ob/ob) and lean mice. Pharmacol Biochem Behav 26:743-747.
29. Calcutt NA, Willars GB, Tomlinson DR. (1988) Axonal transport of choline acetyltransferase and 6-phosphofructokinase activities in genetically diabetic mice. Muscle Nerve 11:1206-1210.
30. Campfield LA, Smith FJ, Guisez Y, et al. (1995) Recombinant mouse OB protein: Evidence for a peripheral signal linking adiposity and central neural networks. Science 269:546-549.
31. Cancello R, Zingaretti MC, Sarzani R, et al. (1998) Leptin and UCP1 genes are reciprocally regulated in brown adipose tissue. Endocrinology 139:4747-4750.
32. Carlisle HJ, Dubuc PU. (1984) Temperature preference of genetically obese (ob/ob) mice. Physiol Behav 33:899-902.
33. Carson KA, Bossen EH, Hanker JS. (1980) Peripheral neuropathy in mouse hereditary diabetes mellitus. II. Ultrastructural correlates of degenerative and regenerative changes. Neuropathol Appl Neurobiol 6:361-374.
34. Ceddia RB. (2005) Direct metabolic regulation in skeletal muscle and fat tissue by leptin: Implications for glucose and fatty acids homeostasis. Int J Obesity 29:1175-1183.
35. Chan CB. (1995) Beta-cell stimulus-Secretion coupling defects in rodent models of obesity. Can J Physiol Pharmacol 73:1414-1424.
36. Chandra RK. (1980) Cell-mediated immunity in genetically obese C57BL/6J ob/ob mice. Am J Clin Nutr 33:13-16.
37. Chehab FF, Lim ME, Lu R. (1996) Correction of the sterility defect in homozygous obese female mice by treatment with the human recombinant leptin. Nat Genet 12:318-320.
38. Chehab FF, Qiu J, Mounzih K, et al. (2002) Leptin and reproduction. Nutr Rev 60:S39-S46; discussion S68-S84, S85-S87.
39. Chen H, Charlat O, Tartaglia LA, et al. (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.
40. Chua S Jr., Liu SM, Li Q, et al. (2002) Differential beta cell responses to hyperglycaemia and insulin resistance in two novel congenic strains of diabetes (FVB-Lepr (db)) and obese (DBA-Lep (ob)) mice. Diabetologia 45:976-990.
41. Chua SC Jr., Liu SM, Li Q, et al. (2004) Transgenic complementation of leptin receptor deficiency. II. Increased leptin receptor transgene dose effects on obesity/diabetes and fertility/lactation in lepr-db/db mice. Am J Physiol 286:E384-E392.
42. Chung WK, Belfi K, Chua M, et al. (1998) Heterozygosity for Lep(ob) or Lep(rdb) affects body composition and leptin homeostasis in adult mice. Am J Physiol 274:R985-R990.
43. Cinti S, Frederich RC, Zingaretti MC, et al. (1997) Immunohistochemical localization of leptin and uncoupling protein in white and brown adipose tissue. Endocrinology 138:797-804.
44. Clee SM, Nadler ST, Attie AD. (2005) Genetic and genomic studies of the BTBR ob/ob mouse model of type 2 diabetes. Am J Ther 12:491-498.
45. Cohen MP, Clements RS, Cohen JA, Shearman CW. (1996) Glycated albumin promotes a generalized vasculopathy in the db/db mouse. Biochem Biophys Res Commun 218:72-75.
46. Cohen P, Zhao C, Cai X, et al. (2001) Selective deletion of leptin receptor in neurons leads to obesity. J Clin Invest 108:1113-1121.
47. Coleman DL. (1973) Effects of parabiosis of obese with diabetes and normal mice. Diabetologia 9:294-298.
48. Coleman DL. (1978) Obese and diabetes: two mutant genes causing diabetes-obesity syndromes in mice. Diabetologia 14:141-148.
49. Coleman DL. (1982) Thermogenesis in diabetes-obesity syndromes in mutant mice. Diabetologia 22:205-211.
50. Coleman DL. (1985) Increased metabolic efficiency in obese mutant mice. Int J Obes 9:Suppl 2, 69-73.
51. Coleman DL. (1992) The influence of genetic background on the expression of mutations at the diabetes (db) locus in the mouse. VI: Hepatic malic enzyme activity is associated with diabetes severity. Metabolism 41:1134-1136.
52. Coleman DL, Hummel KP. (1967) Studies with the mutation, diabetes, in the mouse. Diabetologia 3:238-248.
53. Coleman DL, Hummel KP. (1969a) Effects of parabiosis of normal with genetically diabetic mice. Am J Physiol 217:1298-1304.
54. Coleman DL and Hummel KP. (1969b) The mutation, diabetes, in the mouse. In Diabetes, Proc. VI. Congr. Internat. Diab. Fed. Stockholm, 1967, Internat. Congr. Ser. 172, ed. östman J and Milner RDG, Excerpta med: Amstrdam, 1969b, pp 813-820.
55. Coleman DL, Kuzava JE. (1991) Genetic regulation of malic enzyme activity in the mouse. J Biol Chem 266:21997-22002.
56. Collins S, Surwit RS. (1996) Pharmacologic manipulation of ob expression in a dietary model of obesity. J Biol Chem 271:9437-9440.
57. Collins S, Surwit RS. (2001) The beta-adrenergic receptors and the control of adipose tissue metabolism and thermogenesis. Recent Prog Horm Res 56:309-328.
58. Contaldo F, Gerber H, Coward WA, and Trayhurn P. (1981) Milk intake in pre-weanling genetically obese (ob/ob) mice. In: Obesity: Pathogenesis and Treatment, ed. Enzi G, Crepaldi G, Pozza G, and Renold AE, Academic Press: London and New York, pp. 319-322.
59. Cummings DE, Schwartz MW. (2000) Melanocortins and body weight: A tale of two receptors. Nat Genet 26:8-9.
60. Currie PJ. (1993) Differential effects of NE, CLON, and 5-HT on feeding and macronutrient selection in genetically obese (ob/ob) and lean mice. Brain Res Bull 32:133-142.
61. Currie PJ, Wilson LM. (1993) Potentiation of dark onset feeding in obese mice (genotype ob/ob) following central injection of norepinephrine and clonidine. Eur J Pharmacol 232:227-234.
62. Dardenne M, Savino W, Gastinel LN, et al. (1983) Thymic dysfunction in the mutant diabetic (db/db) mouse. J Immunol 130:1195-1199.
63. Davis RC, Schadt EE, Cervino AC, et al. (2005) Ultrafine mapping of SNPs from mouse strains C57BL/6J, DBA/2J, and C57BLKS/J for loci contributing to diabetes and atherosclerosis susceptibility. Diabetes 54:1191-1199.
64. de Luca C, Kowalski TJ, Zhang Y, et al. (2005) Complete rescue of obesity, diabetes, and infertility in db/db mice by neuron-specific LEPR-B transgenes. J Clin Invest 115:3484-3493.
65. Dhillon H, Zigman JM, Ye C, et al. (2006) Leptin directly activates SF1 neurons in the VMH, and this action by leptin is required for normal body-weight homeostasis. Neuron 49:191-203.
66. Drasher ML, Dickie MM, Lane WD. (1955) Physiological differences in uteri of obese stock mice. A comparison between obese mice and their thin sibs. J Heredity 46:209-212.
67. Drescher VS, Chen HL, Romsos DR. (1994) Corticotropin-releasing hormone decreases feeding, oxygen consumption and activity of genetically obese (ob/ob) and lean mice. J Nutr 124:524-530.
68. Dugail I, Quignard-Boulange A, Le Liepvre X, Lavau M. (1990) Impairment of adipsin expression is secondary to the onset of obesity in db/db mice. J Biol Chem 265:1831-1833.
69. Emilsson V, Liu YL, Cawthorne MA, et al. (1997) Expression of the functional leptin receptor mRNA in pancreatic islets and direct inhibitory action of leptin on insulin secretion. Diabetes 46:313-316.
70. Ewart-Toland A, Mounzih K, Qiu J, Chehab FF. (1999) Effect of the genetic background on the reproduction of leptin-deficient obese mice. Endocrinology 140:732-738.
71. Falconer DS, Isaacson JH. (1959) Adipose, a new inherited obesity of the mouse. J Hered 50:290-292.
72. Fehmann HC, Peiser C, Bode HP, et al. (1997) Leptin: A potent inhibitor of insulin secretion. Peptides 18:1267-1273.
73. Flatt PR, Buchanan KD, Bailey CJ. (1980) Glucagon and diabetes: Evidence for marked insensitivity to local regulation of A-cell function by endogenous insulin in obesehyperglycaemic (ob/ob) mice. Biochem Soc Trans 8:58-59.
74. Flier JS, Cook KS, Usher P, Spiegelman BM. (1987) Severely impaired adipsin expression in genetic and acquired obesity. Science 237:405-408.
75. Frederich RC Jr., Kahn BB, Peach MJ, Flier JS. (1992) Tissue-specific n tritional regulation of angiotensinogen in adipose tissue. Hypertension 19:339-344.
76. Frederich RC, Lollmann B, Hamann A, et al. (1995) Expression of ob mRNA and its encoded protein in rodents. Impact of nutrition and obesity. J Clin Invest 96:658-663.
77. Friedman JM, Halaas JL. (1998) Leptin and the regulation of body weight in mammals. Nature 395:763-770.
78. Fruhbeck G. (2006) Intracellular signaling pathways activated by leptin. Biochem J 393:7-20.
79. Garris DR. (1989) Effects of estradiol and progesterone on diabetes-associated utero-ovarian atrophy in C57BL/KsJ (db/db) mutant mice. Anat Rec 225:310-317.
80. Gartner 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.
81. Gavrilova O, Barr V, Marcus-Samuels B, Reitman M. (1997) Hyperleptinemia of pregnancy associated with the appearance of a circulating form of the leptin receptor. J Biol Chem 272:30546-30551.
82. Ghilardi N, Ziegler S, Wiestner A, et al. (1996) Defective STAT signaling by the leptin receptor in diabetic mice. Proc Natl Acad Sci USA 93:6231-6235.
83. Giacomelli F, Wiener J. (1979) Primary myocardial disease in the diabetic mouse. An ultrastructural study. Lab Invest 40:460-473.
84. Giandomenico G, Dellas C, Czekay RP, et al. (2005) The leptin receptor system of human platelets. J Thromb Haemost 3:1042-1049.
85. Goodbody AE, Trayhurn P. (1982) Studies on the activity of brown adipose tissue in suckling, pre-obese, ob/ob mice. Biochim Biophys Acta 680:119-126.
86. Greenberg D, Ackerman SH. (1984) Genetically obese (ob/ob) mice are predisposed to gastric stress ulcers. Behav Neurosci 98:435-440.
87. Guo K, Lukacik P, Papagrigoriou E, et al. (2006) Characterization of human DHRS6, an orphan short chain dehydrogenase/reductase enzyme: A novel cytosolic type 2 r-betahydroxybutyrate dehydrogenase. J Biol Chem 281:10291-10297.
88. Guo KY, Halo P, Leibel RL, Zhang Y. (2004) Effects of obesity on the relationship of leptin mRNA expression and adipocyte size in anatomically distinct fat depots in mice. Am J Physiol 287:R112-R119.
89. Halaas JL, Gajiwala KS, Maffei M, et al. (1995) Weight-reducing effects of the plasma protein encoded by the obese gene. Science 269:543-546.
90. Hanker JS, Ambrose WW, Yates PE, et al. (1980) Peripheral neuropathy in mouse hereditary diabetes mellitus. I. Comparison of neurologic, histologic, and morphometric parameters with dystonic mice. Acta Neuropathol 51:145-153.
91. Harrison DE, Archer JR, Astle CM. (1984) Effects of food restriction on aging: Separation of food intake and adiposity. Proc Natl Acad Sci USA 81:1835-1838.
92. Hausberger FX. (1958) Parabiosis and transplantation experiments in hereditarily obese mice. Anat Rec 130:313.
93. Hellman B, Jacobsson L, Taeljedal IB. (1963) Endocrine activity of the testis in obesehyperglycaemic mice. Acta Endocrinol 44:20-26.
94. Herberg L, Coleman DL. (1977) Laboratory animals exhibiting obesity and diabetes syndromes. Metabolism 26:59-99.
95. Herberg L. (1988) Insulin resistance in abdominal and subcutaneous obesity: comparison of C57BL/6J-ob/ob with New Zealand obese mice. In Frontiers in Diabetes Research. Lessons from Animal Diabetes II. ed. Shafrir E, Renold A. John Libbey: London, 367-373.
96. Herberg L, Leiter EH. (2001) Obesity/diabetes in mice with mutations in the leptin or leptin receptor genes. Animal Models of Diabetes: A Primer. ed. Sima A, Shafrir E. Frontiers in Animal Diabetes Research. Harwood Academic Publishers: Amsterdam, Netherlands, 63-107.
97. Himms-Hagen J. (1985) Defective brown adipose tissue thermogenesis in obese mice. Int J Obesity 9:Suppl 2, 17-24.
98. Ho A, Chin A. (1988) Circadian feeding and drinking patterns of genetically obese mice fed solid chow diet. Physiol Behav 43:651-656.
99. Hogan S, Himms-Hagen J. (1980) Abnormal brown adipose tissue in obese (ob/ob) mice: Response to acclimation to cold. Am J Physiol 239:E301-E309.
100. Hummel KP, Coleman DL, Lane PW. (1972) The influence of genetic background on expression of mutations at the diabetes locus in the mouse. I. C57BL-KsJ and C57BL-6J strains. Biochem Genet 7:1-13.
101. Hummel KP, Dickie MM, Coleman DL. (1966) Diabetes, a new mutation in the mouse. Science 153:1127-1128.
102. Ingalls AM, Dickie MM, Snell GD. (1950) Obese, a new mutation in the house mouse. J Heredity 41:317-318.
103. Ishizuka T, Klepcyk P, Liu S, et al. (1999) Effects of overexpression of human GLUT4 gene on maternal diabetes and fetal growth in spontaneous gestational diabetic C57BLKS/J Lepr(db/+) mice. Diabetes 48:1061-1069.
104. Jo YH, Wiedl D, Role LW. (2005) Cholinergic modulation of appetite-related synapses in mouse lateral hypothalamic slice. J Neurosci 25:1133-1144.
105. Johnson LM, Sidman, RL. (1979) A reproductive endocrine profile in the diabetes (db) mutant mouse. Biol Reprod 20:552-559.
106. Johnson PR, Hirsch J. (1972) Cellularity of adipose depots in six strains of genetically obese mice. J Lipid Res 13:2-11.
107. Jones N, Harrison GA. (1958) Genetically determined obesity and sterility in the mouse. Stud Fert 9:51-61.
108. Kamata K, Kojima S. (1997) Characteristics of contractile responses of aorta to norepinephrine in db/db mice. Res Commun Mol Pathol Pharmacol 96:319-328.
109. Kaplan ML, Trout JR, Leveille GA. (1976) Adipocyte size distribution in ob/ob mice during preobese and obese phases of development. Proc Soc Exp Biol Med 153:476-482.
110. Kaufmann RC, Amankwah KS, Colliver JA, Arbuthnot J. (1987) Diabetic pregnancy. The effect of genetic susceptibility for diabetes on fetal weight. Am J Perinatol 4:72-74.
111. Kerouz NJ, Horsch D, Pons S, Kahn CR. (1997) Differential regulation of insulin receptor substrates-1 and -2 (IRS-1 and IRS-2) and phosphatidylinositol 3-kinase isoforms in liver and muscle of the obese diabetic (ob/ob) mouse. J Clin Invest 100:3164-3172.
112. Khaidar A, Marx M, Lubec B, Lubec G. (1994) L-arginine reduces heart collagen accumulation in the diabetic db/db mouse. Circulation 90:479-483.
113. Kieffer TJ, Heller RS, Habener JF. (1996) Leptin receptors expressed on pancreatic beta-cells. Biochem Biophys Res Commun 224:522-527.
114. Kieffer TJ, Heller RS, Leech CA, et al. (1997) Leptin suppression of insulin secretion by the activation of ATP-sensitive K+ channels in pancreatic beta-cells. Diabetes 46:1087-1093.
115. Kim JH, Nishina PM, Naggert JK. (1998) Genetic models for non insulin dependent diabetes mellitus in rodents. J Basic Clin Physiol Pharmacol 9:325-345.
116. Kim JH, Taylor PN, Young D, et al. (2003) New leptin receptor mutations in mice: Lepr(dbrtnd), Lepr(db-dmpg) and Lepr(db-rlpy). J Nutr 133:1265-1271.
117. Klebanov S, Astle CM, DeSimone O, et al. (2005) Adipose tissue transplantation protects ob/ob mice from obesity, normalizes insulin sensitivity and restores fertility. J Endocrinol 186:203-211.
118. Konstantinides S, Schafer K, Koschnick S, Loskutoff DJ. (2001) Leptin-dependent platelet aggregation and arterial thrombosis suggests a mechanism for atherothrombotic disease in obesity. J Clin Invest 108:1533-1540.
119. Konstantinides S, Schafer K, Neels JG, et al. (2004) Inhibition of endogenous leptin protects mice from arterial and venous thrombosis. Arterioscler Thromb Vasc Biol 24:2196-2201.
120. Kowalski TJ, Liu SM, Leibel RL, Chua SC Jr. (2001) Transgenic complementation of leptinreceptor deficiency. I. Rescue of the obesity/diabetes phenotype of LEPR-null mice expressing a LEPR-B transgene. Diabetes 50:425-435.
121. Kuhn CM, Cochrane C, Feinglos MN. Surwit, RS. (1987) Exaggerated peripheral responses to catecholamines contribute to stress-induced hyperglycemia in the ob/ob mouse. Pharmacol Biochem Behav 26:491-495.
122. Kulkarni RN, Wang ZL, Wang RM, et al. (1997) Leptin rapidly suppresses insulin release from insulinoma cells, rat and human islets and, in vivo, in mice. J Clin Invest 100:2729-2736.
123. Kuo TH, Giacomelli F, Wiener J, Lapanowski-Netzel K. (1985) Pyruvate dehydrogenase activity in cardiac mitochondria from genetically diabetic mice. Diabetes 34:1075-1081.
124. Kuo TH, Moore KH, Giacomelli F, Wiener J. (1983) Defective oxidative metabolism of heart mitochondria from genetically diabetic mice. Diabetes 32:781-787.
125. La Cava A, Alviggi C, Matarese G. (2004) Unraveling the multiple roles of leptin in inflammation and autoimmunity. J Mol Med 82:4-11.
126. Lane PW. (1959) The pituitary-gonad response of genetically obese mice in parabiosis with thin and obese siblings. Endocrinology 65:863-868.
127. Lane PW, Dickie MM. (1954) Fertile, obese male mice. Relative sterility on obese males corrected by dietary restricion. J Hered 45:56-58.
128. Lee CH, Chen YG, Chen J, et al. (2006) Novel leptin receptor mutation in NOD/LtJ mice suppresses type 1 diabetes progression: II. Immunologic analysis. Diabetes 55:171-178.
129. Lee CH, Reifsnyder PC, Naggert JK, et al. (2005) Novel leptin receptor mutation in NOD/LtJ mice suppresses type 1 diabetes progression: Pathophysiological analysis. Diabetes 54:2525-2532.
130. Lee G, Li C, Montez J, et al. (1997) Leptin receptor mutations in 129 db3J/db3J mice and NIH facp/facp rats. Mamm Genome 8:445-447.
131. Lee GH, Proenca R, Montez JM, et al. (1996) Abnormal splicing of the leptin receptor in diabetic mice. Nature 379:632-635.
132. Lee SM, Bressler R. (1981) Prevention of diabetic nephropathy by diet control in the db/db mouse. Diabetes 30:106-111.
133. Lee SM, Graham A. (1980) Early immunopathologic events in experimental diabetic nephropathy: A study in db/db mice. Exp Mol Pathol 33:323-332.
134. Lee SM, Tutwiler G, Bressler R, Kircher CH. (1982) Metabolic control of prevention of nephropathy by 2-tetradecylglycidate in the diabetic mouse (db/db). Diabetes 31:12-18.
135. Leiter EH, Chapman HD. (1994) Obesity-induced diabetes (diabesity) in C57BL/KsJ mice produces aberrant transregulation of sex steroid sulfotransferase genes. J Clin Invest 93:2007-2013.
136. Leiter EH, Coleman DL, Ingram DK, Reynolds MA. (1983) Influence of dietary carbohydrate on the induction of diabetes in C57BL/KsJ-db/db diabetes mice. J Nutr 113:184-195.
137. Leiter EH, Fewell JW, Kuff EL. (1986) Glucose induces intracisternal type A retroviral gene transcription and translation in pancreatic beta cells. J Exp Med 163:87-100.
138. Leiter EH, Herberg L. (1997) The polygenetics of diabesity in mice. Diabetes Rev 5:131-148.
139. Leiter EH, Kintner J, Flurkey K, et al. (1999) Physiologic and endocrinologic characterization of male sex-biased diabetes in C57BLKS/J mice congenic for the fat mutation at the carboxypeptidease E locus. Endocrine 10:57-66.
140. Leiter EH, Le PH, Coleman DL. (1987) Susceptibility to db gene and streptozotocin-induced diabetes in C57BL mice: Control by gender-associated, MHC-unlinked traits. Immunogenetics 26:6-13.
141. Leiter EH, Prochazka M, Shultz LD. (1987) Effect of immunodeficiency on diabetogenesis in genetically diabetic (db/db) mice. J Immunol 138:3224-3229.
142. Levine AS, Morley JE, Brown DM, Handwerger BS. (1982) Extreme sensitivity of diabetic mice to naloxone-induced suppression of food intake. Physiol Behav 28:987-989.
143. 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.
144. Lubec B, Aufricht C, Herkner K, et al. (1994) Creatine reduces collagen accumulation in the kidneys of diabetic db/db mice. Nephron 67:214-217.
145. Ludwig DS, Tritos NA, Mastaitis JW, et al. (2001) Melanin-concentrating hormone overexpression in transgenic mice leads to obesity and insulin resistance. J Clin Invest 107:379-386.
146. Luo N, Liu SM, Liu H, et al. (2006) Allelic variation on chromosome 5 controls beta cell mass expansion during hyperglycemia in leptin receptor deficient diabetes mice. Endocrinology. In press.
147. MacDougald OA, Hwang CS, Fan H, Lane MD. (1995) Regulated expression of the obese gene product (leptin) in white adipose tissue and 3T3-L1 adipocytes. Proc Natl Acad Sci USA 92:9034-9037.
148. Maffei M, Fei H, Lee GH, et al. (1995) Increased expression in adipocytes of ob RNA in mice with lesions of the hypothalamus and with mutations at the db locus. Proc Natl Acad Sci USA 92:6957-6960.
149. Maffei M, Halaas J, Ravussin E, et al. (1995) Leptin levels in human and rodent: measurement of plasma leptin and ob RNA in obese and weight-reduced subjects. Nat Med 1:1155-1161.
150. Marx M, Trittenwein G, Aufricht C, et al. (1995) Agmatine and spermidine reduce collagen accumulation in kidneys of diabetic db/db mice. Nephron 69:155-158.
151. Matarese G, Carrieri PB, La Cava A, et al. (2005) Leptin increase in multiple sclerosis associates with reduced number of CD4(+)CD25+ regulatory T cells. Proc Natl Acad Sci USA 102:5150-5155.
152. Matarese G, Di Giacomo A, Sanna V, et al. (2001) Requirement for leptin in the induction and progression of autoimmune encephalomyelitis. J Immunol 166:5909-5916.
153. Matarese G, Sanna V, Di Giacomo A, et al. (2001) Leptin potentiates experimental autoimmune encephalomyelitis in SJL female mice and confers susceptibility to males. Eur J Immunol 31:1324-1332.
154. Matarese G, Sanna V, Lechler RI, et al. (2002) Leptin accelerates autoimmune diabetes in female NOD mice. Diabetes 51:1356-1361.
155. Mayer J, Dickie MM, Bates MW, Vitale JJ. (1951) Free selection of nutrients by hereditarily obese mice. Science 113:745-746.
156. McIntosh CHS, Pederson RA (1999) Noninsulin-dependent animal models of diabetes mellitus. In: Experimental Models of Diabetes. ed. McNeill JH, CRC Press LLC, Boca Raton, pp. 338-398.
157. McMinn JE, Liu SM, Dragatsis I, et al. (2004) An allelic series for the leptin receptor gene generated by CRE and FLP recombinase. Mamm Genome 15:677-685.
158. McMinn JE, Liu SM, Liu H, et al. (2005) Neuronal deletion of Lepr elicits diabesity in mice without affecting cold tolerance or fertility. Am J Physiol 289:E403-E411.
159. Meade CJ, Ashwell M, Sowter C. (1979) Is genetically transmitted obesity due to an adipose tissue defect? Proc R Soc Lond B Biol Sci 205:395-410.
160. Meade CJ, Brandon DR, Smith W, et al. (1981) The relationship between hyperglycaemia and renal immune complex deposition in mice with inherited diabetes. Clin Exp Immunol 43:109-120.
161. Memon RA, Fuller J, Moser AH, et al. (1999) Regulation of putative fatty acid transporters and Acyl-CoA synthetase in liver and adipose tissue in ob/ob mice. Diabetes 48:121-127.
162. Memon RA, Grunfeld C, Moser AH, Feingold KR. (1994) Fatty acid synthesis in obese insulin resistant diabetic mice. Horm Metab Res 26:85-87.
163. Midena E, Segato T, Radin S, et al. (1989) Studies on the retina of the diabetic db/db mouse. I. Endothelial cell-pericyte ratio. Ophthalmic Res 21:106-111.
164. Minokoshi Y, Kim YB, Peroni OD, et al. (2002) Leptin stimulates fatty-acid oxidation by activating AMP-activated protein kinase. Nature 415:339-343.
165. Mizuno TM, Bergen H, Funabashi T, et al. (1996) Obese gene expression: reduction by fasting and stimulation by insulin and glucose in lean mice, and persistent elevation in acquired (diet-induced) and genetic (yellow agouti) obesity. Proc Natl Acad Sci USA 93:3434-3438.
166. Moinat M, Deng C, Muzzin P, Assimacopoulos-Jeannet F, Seydoux J, Dulloo AG, et al. (1995) Modulation of obese gene expression in rat brown and white adipose tissues. FEBS Lett 373:131-134.
167. Moon BC, Friedman JM. (1997) The molecular basis of the obese mutation in ob2J mice. Genomics 42:152-156.
168. Morton GJ, Schwartz MW. (2001) The NPY/AgRP neuron and energy homeostasis. Int J Obesity 25:Suppl 5, S56-S62.
169. Mu JL, Naggert JK, Svenson KL, et al. (1999) Quantitative trait loci analysis for the differences in susceptibility to atherosclerosis and diabetes between inbred mouse strains C57BL/6J and C57BLKS/J. J Lipid Res 40:1328-1335.
170. Munzberg H, Flier JS, Bjorbaek C. (2004) Region-specific leptin resistance within the hypothalamus of diet-induced obese mice. Endocrinology 145:4880-4889.
171. Muzumdar R, Ma X, Yang X, et al. (2003) Physiologic effect of leptin on insulin secretion is mediated mainly through central mechanisms. FASEB J 17:1130-1132.
172. Naggert JK, Mu JL, Frankel W, et al. (1995) Genomic analysis of the C57BL/Ks mouse strain. Mamm Genome 6:131-133.
173. Nakata M, Yada T, Soejima N, Maruyama I. (1999) Leptin promotes aggregation of human platelets via the long form of its receptor. Diabetes 48:426-429.
174. Nishimura M, Miyamoto H. (1987) Immunopathological influence of the Ay, db, ob and nu genes placed on the inbred NOD background as murine models for human type I diabetes. J Immunogenet 14:127-130.
175. Nishina PM, Lowe S, Wang J, Paigen B. (1994) Characterization of plasma lipids in genetically obese mice: The mutants obese, diabetes, fat, tubby, and lethal yellow. Metabolism 43:549-553.
176. Nishina PM, Naggert JK, Verstuyft J, Paigen B. (1994) Atherosclerosis in genetically obese mice: The mutants obese, diabetes, fat, tubby, and lethal yellow. Metabolism 43:554-558.
177. Norido F, Canella R, Zanoni R, Gorio A. (1984) Development of diabetic neuropathy in the C57BL/Ks (db/db) mouse and its treatment with gangliosides. Exp Neurol 83:221-232.
178. Ogawa Y, Nakao K. (2000) [Transgenic skinny mice overexpressing leptin]. Seikagaku 72:554-558.
179. Ogus S, Ke Y, Qiu J, Wang B, Chehab FF. (2003) Hyperleptinemia precipitates diet-induced obesity in transgenic mice overexpressing leptin. Endocrinology 144:2865-2869.
180. Pelleymounter MA, Cullen MJ, Baker MB, et al. (1995) Effects of the obese gene product on body weight regulation in ob/ob mice. Science 269:540-543.
181. Poitout, V, Rouault C, Guerre-Millo M, et al. (1998) Inhibition of insulin secretion by leptin in normal rodent islets of Langerhans. Endocrinology 139:822-826.
182. Prochazka M, Premdas FH, Leiter EH, Lipson LG. (1986) Estrone treatment dissociates primary vs. secondary consequences of “diabetes” (db) gene expression in mice. Diabetes 35:725-728.
183. Qiu J, Ogus S, Lu R, Chehab FF. (2001) Transgenic mice overexpressing leptin accumulate adipose mass at an older, but not younger, age. Endocrinology 142:348-358.
184. Qiu J, Ogus S, Mounzih K, et al. (2001) Leptin-deficient mice backcrossed to the BALB/cJ genetic background have reduced adiposity, enhanced fertility, normal body temperature, and severe diabetes. Endocrinology 142:3421-3425.
185. Reddy S, Lau EM, Ross JM. (2004) Immunohistochemical demonstration of leptin in pancreatic islets of nonobese diabetic and CD-1 mice: Colocalization in glucagon cells and its attenuation at the onset of diabetes. J Mol Histol 35:511-519.
186. Reichart U, Kappler R, Scherthan H, et al. (2000) Partial leptin receptor gene deletion in transgenic mice prevents expression of the membrane-bound isoforms except for Ob-Rc. Biochem Biophys Res Commun 269:496-501.
187. Reichling S, Patel HV, Freeman KB, et al. (1988) Attenuated cold-induced increase in mRNA for uncoupling protein in brown adipose tissue of obese (ob/ob) mice. Biochem Cell Biol 66:193-198.
188. Renold AE, Porte D, Shafrir E. (1988) Definitions for diabetes types: Use and abuse of the concept “animal models of diabetes mellitus.” In Lessons from animal diabetes, ed. Shafrir E, Renold AE. J. Libbey, London, 3-7.
189. Robertson DM, Sima AA. (1980) Diabetic neuropathy in the mutant mouse [C57BL/ks(db/db)]: A morphometric study. Diabetes 29:60-67.
190. Roduit R, Thorens B. (1997) Inhibition of glucose-induced insulin secretion by long-term pre-exposure of pancreatic islets to leptin. FEBS Lett 415:179-182.
191. Runner MN. (1954) Inherited hypofunction of the female pituitary in the sterile-obese syndrome in the mouse. Rec Genet Soc Am 23:63-64.
192. Runner MN, Gates A. (1954) Sterile, obese mothers. J Heredity 45:51-55.
193. Segal-Lieberman G, Bradley RL, Kokkotou E, et al. (2003) Melanin-concentrating hormone is a critical mediator of the leptin-deficient phenotype. Proc Natl Acad Sci USA 100:10085-10090.
194. Seufert J, Kieffer TJ, Leech CA, et al. (1999) Leptin suppression of insulin secretion and gene expression in human pancreatic islets: Implications for the development of adipogenic diabetes mellitus. J Clin Endocrinol Metab 84:670-676.
195. Shafrir E. (1992) Animal models of non-insulin dependent diabetes. Diabetes/Metabolism Rev 8:179-208.
196. Sheena J, Meade CJ. (1978) Mice bearing the ob/ob mutation have impaired immunity. Int Arch Allergy Appl Immunol 57:263-268.
197. Shimada M, Tritos NA, Lowell BB, et al. (1998) Mice lacking melanin-concentrating hormone are hypophagic and lean. Nature 396:670-674.
198. Shimomura Y, Oku J, Glick Z, Bray GA. (1982) Opiate receptors, food intake and obesity. Physiol Behav 28:441-445.
199. Sima AA, Robertson DM. (1979) Peripheral neuropathy in the diabetic mutant mouse. An ultrastructural study. Lab Invest 40:627-632.
200. Simpson ER, Merrill JC, Hollub AJ, et al. (1989) Regulation of estrogen biosynthesis by human adipose cells. Endocr Rev 10:136-148.
201. Skoza L, Giacomelli F, Wiener J. (1980) Lysosomal enzymes in the heart of the genetically diabetic mouse. Lab Invest 43:443-448.
202. Smithberg M, Runner MN. (1957) Pregnancy induced in genetically sterile mice. J Heredity 48:97-100.
203. Sprott RL. (1972) Long-term studies of feeding behavior of obese, diabetic, and viable yellow mutant mice under ad lib and operant conditions. Psychol Rep 30:991-1003.
204. Stephens TW, Basinski M, Bristow PK, et al. (1995) The role of neuropeptide Y in the antiobesity action of the obese gene product. Nature 377:530-532.
205. Stern JS, Hirsch J, Drewnowski A, et al. (1983) Glycerol kinase activity in adipose tissue of obese rats and mice: Effects of diet composition. J Nutr 113:714-720.
206. Stoehr JP, Byers JE, Clee SM, et al. (2004) Identification of major quantitative trait loci controling body weight variation in ob/ob mice. Diabetes 53:245-249.
207. Stoehr JP, Nadler ST, Schueler KL, et al. (2000) Genetic obesity unmasks nonlinear interactions between murine type 2 diabetes susceptibility loci. Diabetes 49:1946-1954.
208. Strohmayer AJ, Smith GP. (1987) The meal pattern of genetically obese (ob/ob) mice. Appetite 8:111-123.
209. Suganami T, Mukoyama M, Mor, K, et al. (2005) Prevention and reversal of renal injury by leptin in a new mouse model of diabetic nephropathy. FASEB J 19:127-129.
210. Surwit R, Seldin M, Kuhn C, et al. (1994) Diet-induced obesity and diabetes in C57BL/6J and C57BL/KsJ mice. Mouse Genome 92:523-525.
211. Surwit RS, Williams PG. (1996) Animal models provide insight into psychosomatic factors in diabetes. Psychosom Med 58:582-589.
212. Swenne I, Andersson A. (1984) Effect of genetic background on the capacity for islet cell replication in mice. Diabetologia 27:464-467.
213. Swerdloff RS, Batt RA, Bray GA. (1976) Reproductive hormonal function in the genetically obese (ob/ob) mouse. Endocrinology 98:1359-1364.
214. Swerdloff RS, Peterson M, Vera A, et al. (1978) The hypothalamic-pituitary axis in genetically obese (ob/ob) mice: Response to luteinizing hormone-releasing hormone. Endocrinology 103:542-547.
215. Tanaka T, Hidaka S, Masuzaki H, et al. (2005) Skeletal muscle AMP-activated protein kinase phosphorylation parallels metabolic phenotype in leptin transgenic mice under dietary modification. Diabetes 54:2365-2374.
216. Tartaglia LA, Dembski M, Weng X, et al. (1995) Identification and expression cloning of a leptin receptor, OB-R. Cell 83:1263-1271.
217. Thurlby PL, Trayhurn P. (1978) The development of obesity in preweaning ob/ob mice. Br J Nutr 39:397-402.
218. Thurlby PL, Trayhurn P. (1979) The role of thermoregulatory thermogenesis in the development of obesity in genetically obese (ob/ob) mice pair-fed with lean siblings. Br J Nutr 42:377-385.
219. Togawa K, Moritani M, Yaguchi H, Itakura M. (2006) Multidimensional genome scans identify the combinations of genetic loci linked to diabetes-related phenotypes in mice. Hum Mol Genet 15:113-128.
220. Toye AA, Lippiat JD, Proks P, et al. (2005) A genetic and physiological study of impaired glucose homeostasis control in C57BL/6J mice. Diabetologia 48:675-686.
221. Trayhurn P. (1979) Thermoregulation in the diabetic-obese (db/db) mouse. The role of nonshivering thermogenesis in energy balance. Pflugers Arch 380:227-232.
222. Trayhurn P, Duncan JS, Hoggard N, Rayner DV. (1998) Regulation of leptin production: A dominant role for the sympathetic nervous system? Proc Nutr Soc 57:413-439.
223. Trayhurn P, James WP. (1978) Thermoregulation and non-shivering thermogenesis in the genetically obese (ob/ob) mouse. Pflugers Arch 373:189-193.
224. Trayhurn P, Jones PM, McGuckin MM, Goodbody AE. (1982) Effects of overfeeding on energy balance and brown fat thermogenesis in obese (ob/ob) mice. Nature 295:323-325.
225. Trayhurn P, Thomas ME, Duncan JS, Rayner DV. (1995) Effects of fasting and refeeding on ob gene expression in white adipose tissue of lean and obese (ob/ob) mice. FEBS Lett 368:488-490.
226. Trayhurn P, Wood IS. (2005) Signaling role of adipose tissue: Adipokines and inflammation in obesity. Biochem Soc Trans 33:1078-1081.
227. Vicario PP, Slater EE, Saperstein R. (1989) The effect of ponalrestat on sorbitol levels in the lens of obese and diabetic mice. Biochem Int 19:553-561.
228. Vitadello M, Couraud JY, Hassig R, et al. (1983) Axonal transport of acetylcholinesterase in the diabetic mutant mouse. Exp Neurol 82:143-147.
229. Wang Z, Jiang T, Li J, et al. (2005) Regulation of renal lipid metabolism, lipid accumulation, and glomerulosclerosis in FVB db/db mice with type 2 diabetes. Diabetes 54:2328-2335.
230. Weide LG, Lacy PE. (1991) Hereditary hydronephrosis in C57BL/KsJ mice. Lab Anim 41:415-418.
231. Weigle DS, Bukowski TR, Foster DC, et al. (1995) Recombinant ob protein reduces feeding and body weight in the ob/ob mouse. J Clin Invest 96:2065-2070.
232. Weisberg SP, Hunter D, Huber R, et al. (2006) CCR2 modulates inflammatory and metabolic effects of high-fat feeding. J Clin Invest 116:115-124.
233. Weisberg SP, McCann D, Desai M, et al. (2003) Obesity is associated with macrophage accumulation in adipose tissue. J Clin Invest 112:1796-1808.
234. Wencel HE, Smothers C, Opara EC, et al. (1995) Impaired second phase insulin response of diabetes-prone C57BL/6J mouse islets. Physiol Behav 57:1215-1220.
235. Weninger M, Xi Z, Lubec B, et al. (1992) L-arginine reduces glomerular basement membrane collagen N epsilon-carboxymethyllysine in the diabetic db/db mouse. Nephron 62:80-83.
236. Wilkinson M, Moger WH. (1981) Transpubertal modulation of pituitary and testicular function in the ob/ob mouse. Horm Res 14:95-103.
237. Wilson LM, Sinha HL. (1985) Thermal preference behavior of genetically obese (ob/ob) and genetically lean (+/?) mice. Physiol Behav 35:545-548.
238. Wolf G, Schroeder R, Thaiss F, et al. (1998) Glomerular expression of p27Kip1 in diabetic db/db mouse: Role of hyperglycemia. Kidney Int 53:869-879.
239. Xu AW, Kaelin CB, Takeda K, et al. (2005) PI3K integrates the action of insulin and leptin on hypothalamic neurons. J Clin Invest 115:951-958.
240. Yen TT, Acton JM. (1972) Locomotor activity of various types of genetically obese mice. Proc Soc Exp Biol Med 140:647-650.
241. Zhang Y, Olbort M, Schwarzer K, et al. (1997) The leptin receptor mediates apparent autocrine regulation of leptin gene expression. Biochem Biophys Res Commun 240:492-495.
242. Zhang Y, Proenca R, Maffei M, et al. (1994) Positional cloning of the mouse obese gene and its human homologue. Nature 372:425-432.
243. Zheng S, Noonan WT, Metreveli NS, et al. (2004) Development of late-stage diabetic nephropathy in OVE26 diabetic mice. Diabetes 53:248-257.
244. Ziyadeh FN, Cohen MP, Guo J, Jin Y. (1997) RAGE mRNA expression in the diabetic mouse kidney. Mol Cell Biochem 170:147-152.