本文選題：脊髓小腦性共濟失調(diào) + 線蟲�。� 參考：《中南大學》2014年碩士論文

【摘要】：背景：脊髓小腦性共濟失調(diào)(Spinocerebellar ataxia, SCA)是一組具有高度臨床和遺傳異質(zhì)性的常染色體顯性遺傳性神經(jīng)系統(tǒng)退行性疾病。其臨床癥狀以小腦性共濟失調(diào)為主要特征。目前,已至少有20個SCAs的致病基因被定位克隆。但是這些致病基因在SCAs的發(fā)病機制中的具體作用仍不十分清楚。SCA3(亦稱為Machado-Joseph病)是世界范圍內(nèi)最常見的SCA亞型,其發(fā)病主要是由于致病基因ataxin-3的C末端發(fā)生多聚谷氨酰胺數(shù)目的異常擴增引起。為了進一步了解ataxin-3的正常生理功能,我們對ataxin-3的線蟲同源基因atx-3在壽命調(diào)節(jié)和應激抵抗中的作用進行了研究,并探索其與胰島素-胰島素樣生長因子1信號通路(IIS)的關系。 方法：我們構建了chn-1(by155); atx-3(gk193)雙突變線蟲(chn-1為熱休克蛋白同源蛋白70羧基端作用蛋白編碼基因CHIP的線蟲同源基因,CHIP突變可導致常染色體隱性遺傳小腦性共濟失調(diào))；隨后,分別檢測了N2野生型,chn-1(by155),atx-3(gkl93) chn-1(by155);atx-3(gkl93)4種品系線蟲在20℃和35℃熱休克條件下的壽命和運動能力；同時我們利用上述4種品系線蟲通過雜交獲得包含daf-2(e1370)或daf-16(m26)的IIS相關雜交線蟲,并分別檢測了其在20℃和35℃熱休克條件下的壽命和運動能力。 結(jié)果：我們發(fā)現(xiàn)N2,chn-1(by155), atx-3(gk193)chn-1(by155);atx-3(gk193)4種品系線蟲在20℃的壽命和運動能力沒有顯著差異；在熱休克情況下,chn-1突變線蟲表現(xiàn)出壽命縮短和運動衰退的表型,而atx-3突變可以提高chn-1突變線蟲的壽命和運動能力；在熱休克情況下,daf-2突變明顯提高atx-3突變、chn-1突變和atx-3、chn-1雙突變線蟲的壽命和運動能力,而daf-16突變可縮短及減弱atx-3突變和atx-3、chn-1雙突變線蟲的壽命和運動能力,但對chn-1單突變線蟲的表型沒有明顯影響。 結(jié)論:chn-1突變導致線蟲在熱休克條件下的壽命縮短和運動衰退；atx-3突變可挽救chn-1突變線蟲在熱休克條件下的表型；chn-1和atx-3可能通過胰島素-胰島素樣生長因子1信號通路影響線蟲在熱休克條件下的應激抵抗能力;ataxin-3和CHIP突變導致的共濟失調(diào)可能和胰島素-胰島素樣生長因子1信號通路的變化有關。
[Abstract]:Background: spinocerebellar ataxia (SCA) is a group of autosomal dominant neurodegenerative diseases with high clinical and genetic heterogeneity. Its clinical symptoms are mainly characterized by cerebellar ataxia. At present, at least 20 pathogenic genes of as have been located and cloned. But the role of these genes in the pathogenesis of scas remains unclear. SCA3 (also known as Machado-Joseph disease) is the most common SCA subtype worldwide. The pathogenesis was mainly caused by the abnormal amplification of polyglutamine at the C-terminal of the pathogenic gene ataxin-3. In order to further understand the normal physiological function of ataxin-3, we studied the role of atx-3, a nematode homologous gene of ataxin-3, in life regulation and stress resistance, and explored its relationship with insulin-like growth factor-1 signaling pathway. Methods: we constructed chn-1 (by155), atx-3 (gk193) double mutant nematode (Heat-shock protein homologous protein 70 carboxyl terminal protein gene Chip gene mutation), which can lead to autosomal recessive cerebellar ataxia. The life span and mobility of four nematode strains of N _ 2 wild type chn-1 (by155) atx-3 (gkl93) chn-1 (by155) anatx-3 (gkl93) under heat shock at 20 鈩，

本文編號：2114933