Defense Date


Document Type


Degree Name

Master of Science


Human Genetics

First Advisor

Sarah Elsea


Smith-Magenis syndrome (SMS) is a complex disorder caused by haploinsufficiency of RAI1 and characterized by sleep disturbances, behavioral abnormalities, mental retardation, and obesity in teens and adults. Rai1+/- mice are obese after 20 weeks. Dup(17)(p11.2) syndrome is a complex disorder associated with overexpression of RAI1. A transgenic mouse model of dup(17)(p11.2) syndrome overexpresses Rai1 and results in a mouse that is growth delayed. In order to characterize the obese phenotypes of mouse models of SMS and the role of RAI1 in obesity, daily food intake and serum levels of insulin, glucose, PPY, and leptin were measured; adiposity was studied by characterizing fat deposition; and gene expression was studied in the hypothalamus. These studies show that Rai1+/- mice are hyperphagic, consume more during the inactive light phase, and have altered satiety genes in the hypothalamus. Adiposity studies have shown WT females have a higher body fat content and visceral fat proportion than males, but Rai1-Tg and Rai1+/- females have similar fat deposition patterns as WT males. Hypothalamic gene expression studies show that many genes and pathways are affected by Rai1 and Rai1 dosage, including many genes associated with obesity and satiety.


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Is Part Of

VCU University Archives

Is Part Of

VCU Theses and Dissertations

Date of Submission

May 2009