Mutation in the Scyl1 gene encoding amino-terminal kinase-like protein causes a recessive form of spinocerebellar neurodegeneration.
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.
Schmidt
Wolfgang M
WM
Neuromuscular Research Department, Center of Anatomy & Cell Biology, Medical University of Vienna, Währinger Strasse 13, A-1090 Vienna, Austria.
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
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
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