学术报告
题目：Using mouse forward genetics to study disease mechanisms underlying neurodegeneration
报告人： Yichang Jia Ph. D
The Jackson Laboratory, Bar Harbor, ME
时间： Friday 9:00a.m. June 1
地点：生命科学学院411会议室
Although uridine-rich small nuclear RNAs (U-snRNAs) are essential for pre-mRNA splicing, little is known regarding their function in the regulation of alternative splicing or of the biological consequences of their dysfunction in mammals. By using mouse forward genetics, we identified that a mutation in Rnu2-8, one of the mouse multicopy U2 snRNA genes, causes ataxia and neurodegeneration. Coincident with the observed pathology, the level of mutant U2 RNAs was highest in the cerebellum and increased after granule neuron maturation. Furthermore, neuron loss was strongly dependent on the dosage of mutant and wild-type snRNA genes. Comprehensive transcriptome analysis identified a group of alternative splicing events, including the splicing of small introns, which were disrupted in the mutant cerebellum. Our results suggest that the expression of mammalian U2 snRNA genes, previously presumed to be ubiquitous, is spatially and temporally regulated, and dysfunction of a single U2 snRNA causes neuron degeneration through distortion of highly regulated alternative splicing. According to my future work, I am interested in couple questions related to this mutant mice and its disease-associated allele, including how is U2 snRNA involved in alternative splicing regulation and how do global splicing abnormalities cause neurodegeneration? My long term plan is to develop sensitive biomarker for screening for neurodegeneration phenotype by using mouse forward genetics approach.
欢迎各位老师和同学积极参加！