title: The genetic basis of obesity-associated type 2 diabetes (diabesity) in polygenic mouse models.
abstract: Obesity-associated diabetes ("diabesity") in mouse strains is characterized by severe insulin resistance, hyperglycaemia and progressive failure, and loss of beta cells. This condition is observed in inbred obese mouse strains such as the New Zealand Obese (NZO/HlLt and NZO/HlBomDife) or the TALLYHO/JngJ mouse. In lean strains such as C57BLKS/J, BTBR T+tf/J or DBA/2 J carrying diabetes susceptibility genes ("diabetes susceptible" background), it can be induced by introgression of the obesity-causing mutations Lep <ob> (ob) or Lepr <db> (db). Outcross populations of these models have been employed in the genome-wide search for mouse diabetes genes, and have led to positional cloning of the strong candidates Pctp, Tbc1d1, Zfp69, and Ifi202b (NZO-derived obesity) and Sorcs1, Lisch-like, Tomosyn-2, App, Tsc2, and Ube2l6 (obesity caused by the ob or db mutation). Some of these genes have been shown to play a role in the regulation of the human glucose or lipid metabolism. Thus, dissection of the genetic basis of obesity and diabetes in mouse models can identify regulatory mechanisms that are relevant for the human disease.
authors.affiliation: Department of Pharmacology, Department of Experimental Diabetology, German Institute of Human Nutrition Potsdam-Rehbrücke, Arthur-Scheunert-Allee 114-116, 14558, Nuthetal, Germany, joost@dife.de.
authors.forename: Hans-Georg
authors.initials: HG
authors.lastname: Joost
authors.forename: Annette
authors.initials: A
authors.lastname: Schürmann
mesh_terms: D000818:Animals; D001786:Blood Glucose / Q000235:genetics; D003433:Crosses, Genetic; D003924:Diabetes Mellitus, Type 2 / Q000209:etiology*; D004195:Disease Models, Animal; D004843:Epistasis, Genetic; D056726:Genetic Association Studies; D055106:Genome-Wide Association Study; D006706:Homeostasis / Q000235:genetics; D006801:Humans; D024821:Metabolic Syndrome / Q000209:etiology; D051379:Mice; D020412:Multifactorial Inheritance; D009765:Obesity / Q000150:complications* / Q000235:genetics*
chemical_list: D001786:Blood Glucose
references.citation: J Lipid Res. 2012 Aug;53(8):1493-501
references.pmid: 22628617
references.citation: J Diabetes Res. 2013;2013:165327
references.pmid: 23671854
references.citation: Diabetologia. 2000 Dec;43(12):1565-72
references.pmid: 11151768
references.citation: Hum Mol Genet. 2012 Sep 1;21(17):3845-57
references.pmid: 22692684
references.citation: Physiol Genomics. 2009 Jul 9;38(2):226-32
references.pmid: 19470805
references.citation: J Clin Endocrinol Metab. 2008 Nov;93(11 Suppl 1):S37-50
references.pmid: 18987269
references.citation: Nat Genet. 2000 Mar;24(3):221-5
references.pmid: 10700173
references.citation: Physiol Genomics. 2012 Mar 19;44(6):345-51
references.pmid: 22274563
references.citation: Methods Mol Biol. 2012;933:59-73
references.pmid: 22893401
references.citation: J Biol Chem. 1997 Dec 19;272(51):31937-40
references.pmid: 9405382
references.citation: Metabolism. 1977 Jan;26(1):59-99
references.pmid: 834144
references.citation: Nat Rev Genet. 2008 Nov;9(11):819-30
references.pmid: 18852695
references.citation: Physiol Genomics. 2002 Dec 3;11(3):205-17
references.pmid: 12388789
references.citation: Diabetes. 2013 Aug;62(8):2784-95
references.pmid: 23557705
references.citation: Eur J Clin Invest. 2000 Mar;30(3):195-202
references.pmid: 10691995
references.citation: Nat Genet. 2004 Nov;36(11):1133-7
references.pmid: 15514660
references.citation: Int J Obes (Lond). 2007 May;31(5):829-41
references.pmid: 17060928
references.citation: Hum Mol Genet. 2008 Jun 15;17(12):1798-802
references.pmid: 18325908
references.citation: Nat Rev Genet. 2005 Apr;6(4):271-86
references.pmid: 15803197
references.citation: BMC Genet. 2012 Oct 01;13:81
references.pmid: 23025571
references.citation: Sci Signal. 2013 Jul 30;6(286):ra64
references.pmid: 23901139
references.citation: BMC Genomics. 2010 Dec 19;11:713
references.pmid: 21167066
references.citation: PLoS Genet. 2011 Oct;7(10):e1002323
references.pmid: 21998599
references.citation: Physiol Genomics. 2006 Apr 13;25(2):234-41
references.pmid: 16614459
references.citation: Methods Mol Biol. 2012;933:75-87
references.pmid: 22893402
references.citation: Physiol Genomics. 2012 Jan 18;44(1):1-13
references.pmid: 22010005
references.citation: FEBS Lett. 2006 Oct 30;580(25):5953-8
references.pmid: 17046758
references.citation: Mamm Genome. 2004 Jan;15(1):14-22
references.pmid: 14727138
references.citation: PLoS Genet. 2012;8(12):e1003107
references.pmid: 23236292
references.citation: Biochem Biophys Res Commun. 2003 May 16;304(4):812-7
references.pmid: 12727230
references.citation: Metabolism. 2004 Jun;53(6):799-808
references.pmid: 15164332
references.citation: Genome Biol. 2013 Jul 31;14(7):R82
references.pmid: 23902802
references.citation: Genomics. 2001 Jun 15;74(3):273-86
references.pmid: 11414755
references.citation: Genetics. 2011 Feb;187(2):611-21
references.pmid: 21115971
references.citation: Vascul Pharmacol. 2006 Jul;45(1):65-71
references.pmid: 16750656
references.citation: Endocrinology. 2007 Apr;148(4):1561-73
references.pmid: 17194745
references.citation: PLoS Genet. 2009 Jul;5(7):e1000541
references.pmid: 19578398
references.citation: PLoS Genet. 2008 Mar 14;4(3):e1000034
references.pmid: 18369453
references.citation: Diabetes. 1998 Aug;47(8):1287-95
references.pmid: 9703330
references.citation: PLoS Genet. 2008 Jul 25;4(7):e1000137
references.pmid: 18654634
references.citation: Genome Res. 2011 Jul;21(7):1065-73
references.pmid: 21507882
references.citation: Hum Mol Genet. 2006 Sep 15;15(18):2709-20
references.pmid: 16893906
references.citation: Nature. 1994 Dec 1;372(6505):425-32
references.pmid: 7984236
references.citation: Physiol Genomics. 2008 Jun 12;34(1):42-53
references.pmid: 18397992
references.citation: Diabetes. 2000 Sep;49(9):1590-6
references.pmid: 10969845
references.citation: Nat Genet. 2006 Jun;38(6):688-93
references.pmid: 16682971
references.citation: PLoS One. 2013;8(1):e53025
references.pmid: 23308133
references.citation: Diabetologia. 2005 Apr;48(4):675-86
references.pmid: 15729571
references.citation: Nature. 1997 Jan 9;385(6612):119-20
references.pmid: 8990109
references.citation: Diabetologia. 2002 Jun;45(6):823-30
references.pmid: 12107726
references.citation: Nat Genet. 2008 Nov;40(11):1354-9
references.pmid: 18931681
references.citation: Adv Clin Chem. 2009;48:95-109
references.pmid: 19803416
references.citation: Diabetes. 2000 Nov;49(11):1946-54
references.pmid: 11078464
references.citation: Physiol Genomics. 2005 Jul 14;22(2):171-81
references.pmid: 15870394
references.citation: Diabetes. 2002 Mar;51(3):825-32
references.pmid: 11872687
references.citation: Cell Metab. 2013 Jan 8;17(1):141-52
references.pmid: 23312289
references.citation: Genome Res. 2000 Oct;10(10):1568-78
references.pmid: 11042154
references.citation: Diabetologia. 1978 Mar;14(3):141-8
references.pmid: 350680
references.citation: Endocrinology. 1997 Oct;138(10):4234-9
references.pmid: 9322935
references.citation: Endocrinology. 2013 Oct;154(10):3502-14
references.pmid: 23892475
references.citation: Physiol Genomics. 2009 May 13;37(3):294-302
references.pmid: 19336533
references.citation: Nature. 1998 Mar 26;392(6674):398-401
references.pmid: 9537324
references.citation: Methods Mol Biol. 2009;560:1-17
references.pmid: 19504239
references.citation: Metabolism. 1965 Mar;14:271-80
references.pmid: 14261412
references.citation: Endocrinology. 2010 Jan;151(1):96-102
references.pmid: 19906813
references.citation: Diabetes. 2006 Jul;55(7):2153-6
references.pmid: 16804088
references.citation: J Lipid Res. 2012 May;53(5):964-972
references.pmid: 22383686
references.citation: Genome Res. 2008 May;18(5):706-16
references.pmid: 18347327
references.citation: Mamm Genome. 2001 Feb;12(2):95-103
references.pmid: 11210195
references.citation: Endocrinology. 2002 Mar;143(3):775-83
references.pmid: 11861497