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pubmed-article:14749259pubmed:dateCreated2004-1-29lld:pubmed
pubmed-article:14749259pubmed:abstractTextThe genetic basis for the more common forms of human obesity predisposing to insulin resistance and development of type 2 diabetes is multigenic rather than monogenic in origin. New mouse "diabesity" models have been created by combining independent diabetes risk-conferring quantitative trait loci from two unrelated parental strains: New Zealand Obese (NZO/HlLt) and Nonobese Nondiabetic (NON/Lt). F1 hybrid males, heterozygous at all polymorphic autosomal loci distinguishing the two parental strains, are driven to obesity-induced diabetes (diabesity) at high frequencies. This review focuses on two new recombinant congenic strains (RCSs) developed by introgressing multiple NZO/HlLt chromosomal segments into the nominally diabesity-resistant NON/Lt strain background. Both RCSs gain more weight than NON animals. Although exhibiting comparable weight gain and adiposity, only one of the two RCSs develops diabetes. Hence, these two RCSs will be instructive in elucidating genetic and pathophysiological differences underlying uncomplicated obesity syndromes versus diabetogenic obesity (diabesity) syndromes. Unlike mice with null mutations in a single gene producing morbid obesity, the new models develop a more moderate obesity produced by the interaction of numerous genes with relatively small effects. These RCSs are differentially sensitive to adverse side effects of thiazolidinediones and thus should be particularly useful for pharmacogenetic analyses.lld:pubmed
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pubmed-article:14749259pubmed:authorpubmed-author:LeiterEdward...lld:pubmed
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pubmed-article:14749259pubmed:volume53 Suppl 1lld:pubmed
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pubmed-article:14749259pubmed:paginationS4-11lld:pubmed
pubmed-article:14749259pubmed:dateRevised2008-11-21lld:pubmed
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pubmed-article:14749259pubmed:year2004lld:pubmed
pubmed-article:14749259pubmed:articleTitleDifferential levels of diabetogenic stress in two new mouse models of obesity and type 2 diabetes.lld:pubmed
pubmed-article:14749259pubmed:affiliationJackson Laboratory, Bar Harbor, Maine 04609, USA. ehl@jax.orglld:pubmed
pubmed-article:14749259pubmed:publicationTypeJournal Articlelld:pubmed
pubmed-article:14749259pubmed:publicationTypeResearch Support, U.S. Gov't, P.H.S.lld:pubmed
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