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

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    Date
    2016-05
    Author
    Johnson, Kenji
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    Abstract
    Pax6 is a highly conserved transcription factor that is critical for central nervous system development. It is expressed in the eye, forebrain and hindbrain, and spinal cord. It is also expressed in the endocrine cells of the pancreas and GI tract, the islets of Langerhans and enteroendocrine cells, respectively. Many of these functions have been reported by studying the effects of a complete absence of Pax6. However, the complete absence of Pax6, in both humans and mice results in the absence of eyes, deformed nasal cavities, and neonate lethality. Pax6 is semidominant such that a mutation in one copy of the gene results in a congenital condition known as Aniridia in humans. Aniridia is defined by the absence of the iris and the ocular phenotypes of this haplo-insufficiency in Pax6 have been well described. However, less is known about how a heterozygous mutation in Pax6 affects other places where Pax6 is expressed. Recently, Aniridic patients have reported an increased propensity for obesity, infertility, polycystic ovarian disease, and severe eczema. Additionally, several lines of evidence suggest an impact on the brain as well as the gut. In this dissertation, we have attempted to illuminate the impact of Pax6 haplo-insufficiency on the endocrine system, including the previously unexplored impact on the pituitary gland and enteroendocrine cells, as well as in the brain. We found that a haplo-insufficiency in Pax6 results in a decrease in GH-producing cells and increase in TSH-producing cells in neonate mice, with the increased TSH-producing cells continuing in adult pituitary glands. This increase in TSH-producing cells results in an increase in circulating levels of T4, although no significant change in circulating T3 levels were found. We also found that a haplo-insufficiency results in structural changes in the adult cerebellum, hippocampus, olfactory bulb, and slight changes in the anterior commissure. Together, these data show that a haplo-insufficiency in Pax6 impacts development and function of a number of organs where Pax6 is expressed and reveals a role for Pax6 in the endocrine system that has previously been unexplored and provides evidence for further studies for the impact of Pax6 haplo-insufficiency.
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    http://purl.galileo.usg.edu/uga_etd/johnson_kenji_201605_phd
    http://hdl.handle.net/10724/36188
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    • University of Georgia Theses and Dissertations

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