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Journal of Neuroscience, Vol 11, 2295-2302, Copyright © 1991 by Society for Neuroscience

ARTICLE

The Lurcher cerebellar mutant phenotype is not expressed on a staggerer mutant background

A Messer, B Eisenberg and J Plummer
Wadsworth Center for Laboratories and Research, New York State Department of Health, Albany 12201-0509.

The hierarchy of the various processes responsible for the development of the complex, elaborated Purkinje cell can be examined by taking advantage of a series of spontaneous mutations that affect cerebellar development in the mouse. This study uses double mutants containing genes for two separate hereditary cerebellar mutations that have been shown to act intrinsically in Purkinje cells in order to investigate the time course and modes of action of these mutations. Lurcher mice show 100% degeneration of Purkinje cells, starting during the second postnatal week, while staggerer mice show reduced numbers of Purkinje cells in a distinctive mediolateral distribution from the time of birth, with the remainder grossly stunted. When these mutations are combined genetically, mice shown by progeny tests to harbor both staggerer and Lurcher genotypes exhibit staggerer-like behavior and overall cerebellar morphology; they also do not lose 100% of their Purkinje cells, as Lurcher mutants would otherwise do. Instead, they show a characteristic staggerer cerebellar pathology. We conclude that the intrinsic action of the staggerer gene in Purkinje cells occurs earlier in development than do effects of the Lurcher gene, and that the action of the staggerer gene prevents Purkinje cells from acquiring the characteristics required for the cytotoxic action of the Lurcher gene.

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				H. S. Zanjani, M. W. Vogel, J. C. Martinou, N. Delhaye-Bouchaud, and J. Mariani Postnatal Expression of Hu-Bcl-2 Gene in Lurcher Mutant Mice Fails to Rescue Purkinje Cells but Protects Inferior Olivary Neurons from Target-Related Cell Death J. Neurosci., January 1, 1998; 18(1): 319 - 327. [Abstract] [Full Text] [PDF]

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				K Herrup and J. Busser The induction of multiple cell cycle events precedes target-related neuronal death Development, January 8, 1995; 121(8): 2385 - 2395. [Abstract] [PDF]

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