Epistasis between Pax6^Sey and genetic background reinforces the value of defined hybrid mouse models for therapeutic trials.

ABSTRACT: The small eye (Sey) mouse is a model of PAX6-aniridia syndrome (aniridia). Aniridia, a congenital ocular disorder caused by heterozygous loss-of-function mutations in PAX6, needs new vision saving therapies. However, high phenotypic variability in Sey mice makes development of such therapies challenging. We hypothesize that genetic background is a major source of undesirable variability in Sey mice. Here we performed a systematic quantitative examination of anatomical, histological, and molecular phenotypes on the inbred C57BL/6J, hybrid B6129F1, and inbred 129S1/SvImJ backgrounds. The Sey allele significantly reduced eye weight, corneal thickness, PAX6 mRNA and protein levels, and elevated blood glucose levels. Surprisingly, Pax6^Sey/Sey brains had significantly elevated Pax6 tr

SUBMITTER: Hickmott JW 

PROVIDER: S-EPMC6335240 | biostudies-literature | 2018 Dec

REPOSITORIES: biostudies-literature