碩士 / 國立臺灣師範大學 / 生命科學研究所 / 98 / Spinocerebellar ataxia type 12 (SCA12) is associated with CAG repeat expansion of the 5’UTR of PPP2R2B gene isoform 1 (Bβ1), which encodes a brain-specific regulatory subunit of the protein phosphatase 2A (PP2A). SCA12’s pathogenesis was hypothesized that CAG repeat expansion increased PPP2R2B expression, which altered PP2A activity and induced neuronal dysfunction and death. We have established Bβ1 overexpression transgenic mice and found that Purkinje cell loss, gliosis and some emotional alteration were shown in these mice. In this study, we continued characterize these mice. In addition, substrates of PP2A including microtubule-associated protein tau, which has a close connection with Alzheimer’s disease (AD). To have a quick and easy platform for further study the Bβ1 impact on the SCA12 and AD diseases, we tried to establish an adult or young adult slice culture from mouse hippocampus. Slice culture from the Bβ1 transgenic mice enable us to investigate the molecular pathology and screen potential therapeutic compounds for SCA12. Our behavior analysis showed that Bβ1 transgenic mice (line 20) had a better performance in rotarod and lower anxiety in EPM tasks. The only noticeable abnormality of transgenic mice is that they had significant increasing in fecal output during the rotarod analysis. For slice culture, we have successfully established a stable testing platform by using adult mouse hippocampal tissues. We could maintain the slice survival rate over 60% at DIV18. This ex vivo system should enable us to gain more information about the deregulation of Bβ1.
| Identifer | oai:union.ndltd.org:TW/098NTNU5112028 |
| Date | January 2010 |
| Creators | Chih-Kang Ma, 馬智剛 |
| Contributors | Hsiu-Mei Hsieh, 謝秀梅 |
| Source Sets | National Digital Library of Theses and Dissertations in Taiwan |
| Language | zh-TW |
| Detected Language | English |
| Type | 學位論文 ; thesis |
| Format | 69 |
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