Loss of Purkinje cells in the PKCγ H101Y transgenic mouse

Spinocerebellar ataxia type 14 (SCA14) is an autosomal, dominant neurodegenerative disorder caused by mutations in PKC gamma. The objective of this study was to determine effects of PKC gamma H101Y SCAM mutation on Purkinje cells in the transgenic mouse. Results demonstrated that wild type PKC gamma-like Purkinje cell localization of HA-tagged PKCy H101Y mutant proteins, altered morphology and loss of Purkinje cells were observed in the PKCy H101Y SCA14 transgenic mouse at four weeks of age. Failure of stereotypical clasping responses in the hind limbs of transgenic mice was also observed. Further, PKC gamma H101Y SCA14 mutation caused lack of total cellular PKCy enzyme activity, loss of connexin 57 phosphorylation on serines, and activation of caspase-12 in the PKC gamma H101Y SCA14 transgenic mouse. Results clearly demonstrate a need for PI(Cy control of gap junctions for maintenance of Purkinje cells. This is the first transgenic mouse to our knowledge which models a human SCA14 mutation. (C) 2008 Elsevier Inc. All rights reserved.