トランスジェニックマウスを用いた伸長ポリグルタミン鎖によるCREB依存性の転写活性の検討
スポンサーリンク
概要
- 論文の詳細を見る
Dentatorubral-pallidoluysian atrophy (DRPLA) is an autosomal dominant neurodegenerative disorder. Previous studies have shown that DRPLA protein with expanded polyglutamine stretches interact with transcription factors in DRPLA patient's neuron or cultured cell. Furthermore, it suppresses CREB-dependent transcriptional activation in cultured cells. The interference of CREB-dependent transcription by expanded polyglutamine stretches might cause DRPLA. To study the effect of expanded polyglutamine stretches on the CREB-dependent transcriptional activation in vivo, we made transgenic mice harboring a CRE-LacZ reporter gene and a full-length mutant human DRPLA gene with expanded CAG repeats (Q76). We analyzed a correlation between the nuclear accumulation of expanded polyglutamine stretches and CREB-dependent transcriptional activation in each cortical neuron. We found the strong linear correlation between the CREB-dependent transcriptional activation and the amount of DRPLA protein with expanded polyglutamine stretch in nucleus. This activation of CREB-dependent transcription might be a compensatory response to the accumulation of expanded polyglutamine stretches in nucleus.
- 新潟大学の論文
- 2005-11-10