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Previous Article | Next Article
Volume 17, Number 19, Issue of October 1, 1997 pp. 7385-7395
Copyright ©1997 Society for NeurosciencePurkinje Cell Expression of a Mutant Allele of SCA1 in Transgenic Mice Leads to Disparate Effects on Motor Behaviors, Followed by a Progressive Cerebellar Dysfunction and Histological Alterations
Received May 20, 1997; revised July 8, 1997; accepted July 16, 1997.
H. Brent Clark1, 2, Eric N. Burright1, 4, Wael S. Yunis1, Seth Larson1, Claire Wilcox1, Boyd Hartman3, Antoni Matilla5, Huda Y. Zoghbi5, and Harry T. Orr1, 4 Departments of 1 Laboratory Medicine and Pathology, 2 Neurology, and 3 Psychiatry and 4 Institute of Human Genetics, University of Minnesota, Minneapolis, Minnesota 55455, and 5 Departments of Pediatrics and Human Genetics, Howard Hughes Medical Institute, Baylor College of Medicine, Houston, Texas 77030
Spinocerebellar ataxia type 1 (SCA1) is an autosomal dominant neurological disorder caused by the expansion of a CAG repeat encoding a polyglutamine tract. Work presented here describes the behavioral and neuropathological course seen in mutant SCA1 transgenic mice. Behavioral tests indicate that at 5 weeks of age mutant mice have an impaired performance on the rotating rod in the absence of deficits in balance and coordination. In contrast, these mutant SCA1 mice have an increased initial exploratory behavior. Thus, expression of the mutant SCA1 allele within cerebellar Purkinje cells has divergent effects on the motor behavior of juvenile animals: a compromise of rotating rod performance and a simultaneous enhancement of initial exploratory activity. With age, these animals develop incoordination with concomitant progressive Purkinje neuron dendritic and somatic atrophy but relatively little cell loss. Therefore, the eventual development of ataxia caused by the expression of a mutant SCA1 allele is not the result of cell death per se, but the result of cellular dysfunction and morphological alterations that occur before neuronal demise.
Key words: transgenic mice; neurodysfunction; CAG repeat; spinocerebellar ataxia type 1; Purkinje cell; motor behavior
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