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Mutation in the Scyl1 gene encoding amino-terminal kinase-like protein causes a recessive form of spinocerebellar neurodegeneration.

ABSTRACT: Here, we show that the murine neurodegenerative disease mdf (autosomal recessive mouse mutant 'muscle deficient') is caused by a loss-of-function mutation in Scyl1, disrupting the expression of N-terminal kinase-like protein, an evolutionarily conserved putative component of the nucleocytoplasmic transport machinery. Scyl1 is prominently expressed in neurons, and enriched at central nervous system synapses and neuromuscular junctions. We show that the pathology of mdf comprises cerebellar atrophy, Purkinje cell loss and optic nerve atrophy, and therefore defines a new animal model for neurodegenerative diseases with cerebellar involvement in humans.

SUBMITTER: Schmidt WM

PROVIDER: S-EPMC1905899 | biostudies-literature | 2007 Jul

REPOSITORIES: biostudies-literature

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Mutation in the Scyl1 gene encoding amino-terminal kinase-like protein causes a recessive form of spinocerebellar neurodegeneration.

Schmidt Wolfgang M WM Kraus Cornelia C Höger Harald H Hochmeister Sonja S Oberndorfer Felicitas F Branka Manuela M Bingemann Sonja S Lassmann Hans H Müller Markus M Macedo-Souza Lúcia Inês LI Vainzof Mariz M Zatz Mayana M Reis André A Bittner Reginald E RE

EMBO reports 20070615 7

Here, we show that the murine neurodegenerative disease mdf (autosomal recessive mouse mutant 'muscle deficient') is caused by a loss-of-function mutation in Scyl1, disrupting the expression of N-terminal kinase-like protein, an evolutionarily conserved putative component of the nucleocytoplasmic transport machinery. Scyl1 is prominently expressed in neurons, and enriched at central nervous system synapses and neuromuscular junctions. We show that the pathology of mdf comprises cerebellar atroph ...[more]

PMID: 17571074

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