碩士 / 國立陽明大學 / 神經科學研究所 / 97 / Cyclin-dependent kinase 12 (CDK12) is a recently identified CDK that regulates alternative splicing rather than cell cycle progression. Together with its cyclin partners, cyclin L1 and cyclin L2, CDK12 changes the splicing patterns of E1a reporter minigene. The endogenous expression of CDK12 was found abundantly in the nervous system at embryonic stage and gradually decreased as development proceeds. In the mature brain, CDK12 remained its expression in hippocampus. We thus hypothesized that CDK12 activity can maintain neuronal connectivity in adult hippocampus. CDK12 transgenic mouse lines were generated in order to study CDK12 function in vivo. Thy-1 expression cassette was used to carry cDNA of the short isoform of CDK12 (CDK12S) which contains arginine/serine-rich (RS) domain and CDC-like kinase domain. Three transgenic mouse lines, Tg-1, Tg-11 and Tg-17, were obtained and found to carry different copy numbers of the transgene. Analysis of CDK12 by Western blotting showed that the protein expression level is not proportional to the transgene copy number, possibly resulted from different integration sites in genomes of these transgenic lines. Interestingly, expression of transgenic CDK12 protein suppressed amounts of endogenous CDK12 protein in several brain regions, but the total expression of CDK12 was increased. Electrophysiological approaches were then performed to examine changes of synaptic plasticity in CDK12 transgenic mice. Overexpression of CDK12 did not alter LTP induction by a 100 Hz high-frequency stimulus (HFS), but it did lead to LTP induction by a 10 Hz low-frequency stimulus (LFS) which normally has no effect on synaptic plasticity. CDK12 seemed to lower the induction threshold of hippocampal LTP. More experiments are required to determine whether CDK12 regulates synaptic plasticity and what physiological function CDK12 exerts.
| Identifer | oai:union.ndltd.org:TW/097YM005291009 |
| Date | January 2009 |
| Creators | Shen-Yin Chen, 陳聖音 |
| Contributors | Ming-Ji Fann, 范明基 |
| Source Sets | National Digital Library of Theses and Dissertations in Taiwan |
| Language | zh-TW |
| Detected Language | English |
| Type | 學位論文 ; thesis |
| Format | 44 |
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