Deletion (Williams-Beuren syndrome (WBS)) and duplication (Dup7q11.23) of a common interval spanning 26 genes on chromosome 7q11.23 cause disorders with a spectrum of clinical, cognitive and behavioural symptoms. Studies of individuals with atypical deletions have implicated two genes, GTF2IRD1 and GTF2I. Here I describe the behavioural characterization of mice hemizygous for Gtf2i, or Gtf2ird1 and Gtf2i together, as well as mice with additional Gtf2i copies. Dosage changes in Gtf2i were associated with working memory impairment and separation anxiety, and possibly with general anxiety and repetitive behaviours. A potential cause of these phenotypes was found in brain tissue, where subcellular localization of the calcium channel TRPC3, which is regulated by GTF2I, was found to be altered. Collectively, these results provide a better understanding of the contributions of GTF2I to the cognitive and behavioural profile of WBS and Dup7q11.23 and identify a potential biological mechanism that may underlie some of the symptoms.
| Identifer | oai:union.ndltd.org:TORONTO/oai:tspace.library.utoronto.ca:1807/32595 |
| Date | 26 July 2012 |
| Creators | Lam, Emily |
| Contributors | Osborne, Lucy |
| Source Sets | University of Toronto |
| Language | en_ca |
| Detected Language | English |
| Type | Thesis |
Page generated in 0.0017 seconds