Research Abstracts Online
2008 - March 2009
University of Minnesota Twin Cities
Department of Laboratory Medicine and Pathology
PI: Harry T. Orr
Alternative RNA Splicing in SCA1 Mice
Spinocerebellar ataxia type 1 (SCA1) is caused by expansion of a translated CAG repeat that encodes a polyglutamine tract in Ataxin-1. Previous studies demonstrate that a gain-of-function mechanism underlies this disease and the glutamine expansion causes disease only when the protein can be translocated into the nucleus and the serine at position 776 is phosphorylated. Recent studies suggest that the gain-of-function mechanism involves enhanced interactions of ATXN1 with RBM17, a regulator of RNA splicing. These researchers hypothesize that interaction of RBM17 with the mutant ATX1 may cause changes in splicing, which in turn may contribute to onset of the disease. Using exon microarray chips, they have examined the splicing patterns of cerebellar RNA from various mouse models of SCA1. They are using MSI resources such as the Ingenuity Pathway Analysis software to examine pathways that are affected due to alternative splicing between the SCA1 and WT mice. Additionally, they have collaborated with a Biomedical Informatics group at Mayo clinic to develop computational models for deconvolution of the exon array data to analyze the different transcripts generated due to alternative splicing for which MSI’s resources will prove valuable.
Smita Agrawal, Research Associate