genetic basis of obesity-associated type 2 diabetes (diabesity) in polygenic mouse models

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...

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Bibliographic Details
Published in:Mammalian genome 2014-10, Vol.25 (9-10), p.401-412
Main Authors: Joost, Hans-Georg, Schürmann, Annette
Format: Article
Language:English
Subjects:
Animal Genetics and Genomics
animal models
Animals
Biomedical and Life Sciences
Blood Glucose - genetics
Cell Biology
Crosses, Genetic
Diabetes Mellitus, Type 2 - etiology
Disease Models, Animal
Epistasis, Genetic
genes
Genetic Association Studies
Genome-Wide Association Study
glucose
Homeostasis - genetics
human diseases
Human Genetics
Humans
hyperglycemia
insulin resistance
introgression
Life Sciences
lipid metabolism
Metabolic Syndrome - etiology
Mice
molecular cloning
Multifactorial Inheritance
mutation
noninsulin-dependent diabetes mellitus
obesity
Obesity - complications
Obesity - genetics
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Summary: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) or Lepr (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.
ISSN:0938-8990
1432-1777
DOI:10.1007/s00335-014-9514-2