Neuropathological study on transgenic mice with Bβ2 overexpression in the mitochondria

• Main Authors: Chun-Jung Chen, 陳浚榕
• Other Authors: Hsiu-Mei Hsieh
• Format: Others
• Language: en_US
• Published: 2008
• Online Access: http://ndltd.ncl.edu.tw/handle/08653556767293405658

碩士 === 國立臺灣師範大學 === 生命科學研究所 === 96 === Protein phosphatase 2A (PP2A) is a heterotrimeric serine/threonine phosphatase which consists of scaffolding (A), catalytic (C), and variable regulatory (B) subunits. The regulatory B subunits dictate subcellular localization and substrate specificity of the PP2A holoenzyme. The Bβ regulatory subunit gene was reported to be involved in spinocerebellar ataxia type 12 (SCA12). One of the Bβ splice variants, Bβ2, was postulated to target PP2A holoenzyme to mitochondria and promote apoptosis in an in vitro PC12 cell system. To test this hypothesis in vivo, we have established the transgenic mice with Bβ2 overexpression in the mitochondria of neuronal tissues. These transgenic mice show several phenotypical abnormalities, including smaller size, sparse hair, spinal curvature and early lethality. Quantitative motor activity and neuropathological analyses are also conducted to understand the neuronal effect caused by the Bβ2 overexpression in the mitochondria. Our results show that the mitochondria PP2A activity was increased by the Bβ2 overexpression. The cytochrome c releasing, oxidative stress index MnSOD, and apoptotic marker caspase 3 were all significantly up-regulated in the transgenic mice. Behavior performances characterized by Rotarod and HomeCageScan indicate an impairment in neuron function occurred in these animals. Taken together, we suggest that Bβ2 overexpression in the mitochondria of neuronal tissues could induce neuron degeneration.