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Mutation in the Scyl1 gene encoding amino‐terminal kinase‐like protein causes a recessive form of spinocerebellar neurodegeneration
Author(s) -
Schmidt Wolfgang M,
Kraus Cornelia,
Höger Harald,
Hochmeister Sonja,
Oberndorfer Felicitas,
Branka Manuela,
Bingemann Sonja,
Lassmann Hans,
Müller Markus,
MacedoSouza Lúcia Inês,
Vainzof Mariz,
Zatz Mayana,
Reis André,
Bittner Reginald E
Publication year - 2007
Publication title -
embo reports
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.584
H-Index - 184
eISSN - 1469-3178
pISSN - 1469-221X
DOI - 10.1038/sj.embor.7401001
Subject(s) - neurodegeneration , genetics , gene , mutation , biology , terminal (telecommunication) , disease , medicine , computer science , telecommunications , pathology
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.