Characterization of a new transgenic mouse model of theSpinocerebellar Ataxia type 2 disease

ABSTRACT

The objective of this work was the generation of an animal model of the SCA2 disease for future studies on thebenefits of therapeutic molecules and the underlying neuropathological mechanisms in this human disorder. Thetransgenic fragment was microinjected into pronuclei of B6D2F1 X OF1 mouse hybrid strain. For Northern blots,RNAs were hybridized with a human cDNA fragment from the SCA2 gene and a mouse b-actin cDNA fragment.Monoclonal antibodies directed at the N-terminal of the ataxin 2 protein with 22Q were used for Western blotanalysis. A rotating rod apparatus was utilized to measure motor coordination of mice. Immunohistochemicaldetection of Purkinje neurons was performed with anti-calbindin 28K as the primary antibody. An ubiquitousexpression of the SCA2 transgene with 75 CAG repeats regulated by the SCA2 self promoter was obtained afterthe generation of our transgenic mice. The analysis of transgenic mice revealed significant differences of motorcoordination compared with the wild type littermates. A specific degeneration of Purkinje neurons and transgeneover-expression in the brain, liver and skeletal muscle, rather than in lungs and kidneys was also observed, resemblingthe expression pattern of the ataxin 2 in humans...(AU)