title: 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.
authors.affiliation: Neuromuscular Research Department, Center of Anatomy & Cell Biology, Medical University of Vienna, Währinger Strasse 13, A-1090 Vienna, Austria.
authors.forename: Wolfgang M
authors.initials: WM
authors.lastname: Schmidt
authors.forename: Cornelia
authors.initials: C
authors.lastname: Kraus
authors.forename: Harald
authors.initials: H
authors.lastname: Höger
authors.forename: Sonja
authors.initials: S
authors.lastname: Hochmeister
authors.forename: Felicitas
authors.initials: F
authors.lastname: Oberndorfer
authors.forename: Manuela
authors.initials: M
authors.lastname: Branka
authors.forename: Sonja
authors.initials: S
authors.lastname: Bingemann
authors.forename: Hans
authors.initials: H
authors.lastname: Lassmann
authors.forename: Markus
authors.initials: M
authors.lastname: Müller
authors.forename: Lúcia Inês
authors.initials: LI
authors.lastname: Macedo-Souza
authors.forename: Mariz
authors.initials: M
authors.lastname: Vainzof
authors.forename: Mayana
authors.initials: M
authors.lastname: Zatz
authors.forename: André
authors.initials: A
authors.lastname: Reis
authors.forename: Reginald E
authors.initials: RE
authors.lastname: Bittner
mesh_terms: D033942:Adaptor Proteins, Vesicular Transport; D000818:Animals; D003433:Crosses, Genetic; D004268:DNA-Binding Proteins; D005808:Genes, Recessive; D006801:Humans; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D051379:Mice; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D009154:Mutation; D009410:Nerve Degeneration / Q000235:genetics* / Q000473:pathology; D020161:Physical Chromosome Mapping; D011494:Protein Kinases / Q000737:chemistry / Q000235:genetics* / Q000648:ultrastructure; D017434:Protein Structure, Tertiary; D012333:RNA, Messenger / Q000378:metabolism; D020754:Spinocerebellar Ataxias / Q000235:genetics* / Q000473:pathology; D014157:Transcription Factors / Q000235:genetics
chemical_list: D033942:Adaptor Proteins, Vesicular Transport; D004268:DNA-Binding Proteins; D012333:RNA, Messenger; C464929:SCYL1 protein, human; C523633:Scyl1 protein, mouse; D014157:Transcription Factors; D011494:Protein Kinases