Assuntos
Linfócitos T CD8-Positivos/imunologia , Antígenos H-2/imunologia , Ovalbumina/imunologia , Receptores de Antígenos de Linfócitos T alfa-beta/imunologia , Sequência de Aminoácidos , Animais , Linfócitos T CD8-Positivos/metabolismo , Citometria de Fluxo , Antígenos H-2/metabolismo , Camundongos Transgênicos , Ovalbumina/genética , Ovalbumina/metabolismo , Fragmentos de Peptídeos/genética , Fragmentos de Peptídeos/imunologia , Fragmentos de Peptídeos/metabolismo , Reação em Cadeia da Polimerase , Receptores de Antígenos de Linfócitos T alfa-beta/genética , Receptores de Antígenos de Linfócitos T alfa-beta/metabolismo , Especificidade do Receptor de Antígeno de Linfócitos T/imunologiaRESUMO
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.