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Regulation of Sexually Dimorphic RNA Processing Genes in the Developing Mouse Cortex and Hippocampus

<p> My thesis work was to examine the hypothesis that during early development sexually dimorphic expression of the genes associated with RNA processing in the mouse cortex and hippocampus is regulated by perinatal testosterone to activate estrogen receptors (ERs) after its conversion to estradiol via aromatase within the brain, which might create differences in mRNA variants of their targets between the sexes, and then lead to sexual dimorphism in structure and function of these brain regions. To test this, I first used reverse transcriptase with quantitative PCR to measure relative mRNA levels of 14 selected candidate genes, encoding RNA binding proteins, in the cortex/hippocampus of male and female mice collected on the day of birth (PN0), and 7 (PN7), 14 (PN14), and 21 (PN21) days after birth. A significant sex difference in mRNA levels of <i>Khdrbs2, Nanos2, Rbm48</i>, and <i> Tdrd3</i> was observed, and females expressed more <i>Rbm48</i> and <i>Tdrd3</i> mRNA on PN0 and PN7 than males. Of these genes, the female-biased expression of <i>Rbm48</i> in neonates was abolished by prenatal exposure to testosterone propionate via down-regulation of <i> Rbm48</i> mRNA levels in females, but postnatal exposure to testosterone propionate during PN21-23 increased <i>Rbm48</i> expression in both sexes. Surprisingly, neonatal exposure to estradiol benzoate abolished the sex difference in <i>Rbm48</i> expression by up-regulating <i> Rbm48</i> mRNA levels in males. These results suggest that hormonally regulated expression of <i>Rbm48</i> presents a novel molecular mechanism underlying the development of sexual dimorphism in cortical and hippocampal structure and function.</p><p>

Identiferoai:union.ndltd.org:PROQUEST/oai:pqdtoai.proquest.com:10743568
Date10 April 2018
CreatorsFranklin, Michael
PublisherCalifornia State University, Long Beach
Source SetsProQuest.com
LanguageEnglish
Detected LanguageEnglish
Typethesis

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