title: Comparison of Two New Mouse Models of Polygenic Type 2 Diabetes at the Jackson Laboratory, NONcNZO10Lt/J and TALLYHO/JngJ.
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-Lepr(db) (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.
authors.affiliation: The Jackson Laboratory, 600 Main Street, Bar Harbor, ME 04609, USA.
authors.forename: Edward H
authors.initials: EH
authors.lastname: Leiter
authors.forename: Marjorie
authors.initials: M
authors.lastname: Strobel
authors.forename: Adam
authors.initials: A
authors.lastname: O'Neill
authors.forename: David
authors.initials: D
authors.lastname: Schultz
authors.forename: Andrew
authors.initials: A
authors.lastname: Schile
authors.forename: Peter C
authors.initials: PC
authors.lastname: Reifsnyder