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Migration defects of cdk5(-/-) neurons in the developing cerebellum is cell autonomous

By Toshio Ohshima, Edward C. Gilmore, Glenn Longenecker, David M. Jacobowitz, Roscoe O. Brady, Karl Herrup and Ashok B. Kulkarni

Abstract

Cyclin-dependent kinase 5 (Cdk5) is a member of the family of cell cycle-related kinases. Previous neuropathological analysis of cdk5 �/ � mice showed significant changes in CNS development in regions from cerebral cortex to brainstem. Among the defects in these animals, a disruption of the normal pattern of cell migrations in cerebellum was particularly apparent, including a pronounced abnormality in the location of cerebellar Purkinje cells. Complete analysis of this brain region is hampered in the mutant because most of cerebellar morphogenesis occurs after birth and the cdk5 �/ � mice die in the perinatal period. To overcome this disadvantage, we have generated chimeric mice by injection of cdk5 �/ � embryonic stem cells into host blastocysts. Analysis of the cerebellum from the resulting cdk5 �/ � 7 cdk5 �/ � chimeric mice shows that the abnormal location of the mutant Purkinje cells is a cellautonomou

Year: 1999
OAI identifier: oai:CiteSeerX.psu:10.1.1.313.2373
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