Apr 7, 2020

Increased TSH-producing cells in the pituitary gland of Pax6 haploinsufficient mice

BioRxiv : the Preprint Server for Biology
Kenji K Johnson, James D Lauderdale

Abstract

Aniridia is a congenital condition characterized by absence of iris and is caused by a semidominant mutation in the transcription factor encoded by the PAX6 gene. Although ocular phenotypes of this disorder are well characterized, recent studies report that individuals with aniridia have a higher propensity for obesity, infertility, polycystic ovarian disease, and severe eczema compared to their Pax6-normal siblings. These symptoms collectively suggest an underlying endocrine disturbance related to haploinsufficient levels of Pax6. In mice, during development, Pax6 expression in the pituitary gland begins at E9.0 in the primordial anterior pituitary gland (Rathkes Pouch). This expression becomes restricted to the dorsal anterior pituitary by E11.5, but is expressed throughout the anterior lobe by E14.5, and remains through adulthood. It is possible that a reduction in Pax6 could result in a change in pituitary hormone levels or cell numbers, which may explain symptoms experienced by aniridics. Using the Small eye mouse model, we find that Pax6 reduction results in a decrease in GH-producing cells and an increase in TSH-producing cells in neonate mice, with the TSH increase continuing into adulthood. Adult Pax6 haploinsufficient...Continue Reading

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