退化性神經疾病：ＰＰＰ２Ｒ２Ｂ基因族群遺傳分析及分生研究

Neurodegenerative disease:ＰＰＰ２Ｒ２Ｂ gene genetics study and molecular research

侯懿婷(Yi-Ting Hou)

指導教授 ： 李桂楨

國立臺灣師範大學/理學院/生命科學研究所/碩士(2004年)

摘要

無資料

關鍵字

脊髓小腦運動失調症第12型 ； HASH(0x9796840) ； PPP2R2B

並列摘要

The hereditary spinocerebellar ataxias (SCAs) are a group of autosomal dominant adult onset neurodegenerative disorders. Cerebellar dysfunction is a hallmark of all the SCAs, and most also involve other regions of the central or peripheral nervous system. SCA12 is caused by a CAG repeat expansion in the 5' UTR of the PPP2R2B gene. The PPP2R2B gene encodes a brain-specific regulatory subunit Bβ of PP2A (protein phosphotase 2A). Bβ regulates PP2A dephosphorylation activity for specific substrates, including vimentin, histone-1, and tau. The purpose of this study was to determine the genetic and functional roles of the CAG repeat polymorphism within the PPP2R2B gene. The CAG repeat was analyzed in patients with Alzheimer's disease, Parkinson's disease, ataxia, schizophrenia, and healthy controls. The distribution of the alleles in patients was not significantly different from that in the controls, whereas the (CAG)7 allele was significantly overrepresented in the AD patients compared to the controls. The promoter functional assay showed that the deletion of the upstream sequence, but not the downstream sequence of the CAG repeat, reduced the PPP2R2B promoter activity. Expansions of the repeat (49 and 64 triplets) caused a 2~3-fold increase in PPP2R2B promoter activity and the rare (CAG)7 allele displayed 60% activity, as compared to the common 10-, 13-, and 16-triplet alleles, respectively, in human SK-N-SH, LA-N-1, IMR-32, HEK-293 and rat ST14A cells. The upstream sequence of the CAG repeat, but not the CAG repeat or its downstream sequence, was essential for the PPP2R2B transcription. Variations in the CAG repeat number may alter the spacing of flanking promoter elements to influence the expression of PPP2R2B. The (CAG)7 may be a functional polymorphism in the 5' promoter region of PPP2R2B and may be associated with the susceptibility to AD.

並列關鍵字

SCA12

參考文獻

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