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Journal of Diabetes Research
Volume 2013, Article ID 165327, 7 pages
http://dx.doi.org/10.1155/2013/165327
Review Article

Comparison of Two New Mouse Models of Polygenic Type 2 Diabetes at the Jackson Laboratory, NONcNZO10Lt/J and TALLYHO/JngJ

The Jackson Laboratory, 600 Main Street, Bar Harbor, ME 04609, USA

Received 4 February 2013; Accepted 14 March 2013

Academic Editor: Daisuke Koya

Copyright © 2013 Edward H. Leiter et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

This review compares two novel polygenic mouse models of type 2 diabetes (T2D), TALLYHO/JngJ and NONcNZO10/LtJ, and contrasts both with the well-known C57BLKS/J-Leprdb (db/db) monogenic diabesity model. We posit that the new polygenic models are more representative of the “garden variety” obesity underlying human T2D in terms of their polygenetic rather than monogenic etiology. Moreover, the clinical phenotypes in these new models are less extreme, for example, more moderated development of obesity coupled with less extreme endocrine disturbances. The more progressive development of obesity produces a maturity-onset development of hyperglycemia in contrast to the juvenile-onset diabetes observed in the morbidly obese db/db model. Unlike the leptin receptor-deficient db/db models with central leptin resistance, the new models develop a progressive peripheral leptin resistance and are able to maintain reproductive function. Although the T2D pathophysiology in both TALLYHO/JngJ and NONcNZO10/LtJ is remarkably similar, their genetic etiologies are clearly different, underscoring the genetic heterogeneity underlying T2D in humans.