A Drosophila model of the neurodegenerative disease SCA17 reveals a role of RBP-J/Su(H) in modulating the pathological outcome

• DOI: 10.1093/hmg/ddr251
• Publication Date: 2011-06-09T03:34:32Z
• Authors: Jie Ren; Anil G. Jegga; Minlu Zhang; Jingyuan Deng; Junbo Liu; Christopher B. Go...; Bruce J. Aronow; Long J. Lu; Bo Zhang; Jun Ma
• Keywords: Polyglutamine tract

Expanded polyglutamine (polyQ) tract in the human TATA-box-binding protein (hTBP) causes neurodegenerative disease spinocerebellar ataxia 17 (SCA17). To investigate pathological effects of polyQ expansion, we established a SCA17 model Drosophila . Similar to patients, transgenic flies expressing mutant hTBP with an expanded (hTBP80Q) exhibit progressive neurodegeneration, late-onset locomotor impairment and shortened lifespan. Microarray analysis reveals that hTBP80Q widespread time-dependent transcriptional dysregulation In candidate screen for genetic modifiers, identified RBP-J/Su(H), transcription factor contains Q/N-rich domains participates Notch signaling. Knockdown Su(H) by RNAi further enhances hTBP80Q-induced eye defects, whereas overexpression suppresses such defects. While transcript level is not significantly altered hTBP80Q-expressing flies, genes contain Su(H)-binding sites are among those dysregulated. We show interacts more efficiently than wild-type hTBP, suggesting reduction fraction available its normal cellular functions contributes phenotypes. signaling pathway has been implicated several neurological disorders, our study suggests possibility activity nuclear component RBP-J/Su(H) may modulate progression patients.