Document Detail

A point mutation in TRPC3 causes abnormal Purkinje cell development and cerebellar ataxia in moonwalker mice.
MedLine Citation:
PMID:  19351902     Owner:  NLM     Status:  MEDLINE    
The hereditary ataxias are a complex group of neurological disorders characterized by the degeneration of the cerebellum and its associated connections. The molecular mechanisms that trigger the loss of Purkinje cells in this group of diseases remain incompletely understood. Here, we report a previously undescribed dominant mouse model of cerebellar ataxia, moonwalker (Mwk), that displays motor and coordination defects and loss of cerebellar Purkinje cells. Mwk mice harbor a gain-of-function mutation (T635A) in the Trpc3 gene encoding the nonselective transient receptor potential cation channel, type C3 (TRPC3), resulting in altered TRPC3 channel gating. TRPC3 is highly expressed in Purkinje cells during the phase of dendritogenesis. Interestingly, growth and differentiation of Purkinje cell dendritic arbors are profoundly impaired in Mwk mice. Our findings define a previously unknown role for TRPC3 in both dendritic development and survival of Purkinje cells, and provide a unique mechanism underlying cerebellar ataxia.
Esther B E Becker; Peter L Oliver; Maike D Glitsch; Gareth T Banks; Francesca Achilli; Andrea Hardy; Patrick M Nolan; Elizabeth M C Fisher; Kay E Davies
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2009-04-07
Journal Detail:
Title:  Proceedings of the National Academy of Sciences of the United States of America     Volume:  106     ISSN:  1091-6490     ISO Abbreviation:  Proc. Natl. Acad. Sci. U.S.A.     Publication Date:  2009 Apr 
Date Detail:
Created Date:  2009-05-06     Completed Date:  2009-05-29     Revised Date:  2014-02-24    
Medline Journal Info:
Nlm Unique ID:  7505876     Medline TA:  Proc Natl Acad Sci U S A     Country:  United States    
Other Details:
Languages:  eng     Pagination:  6706-11     Citation Subset:  IM    
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MeSH Terms
Amino Acid Sequence
Cell Differentiation
Cerebellar Ataxia / pathology*,  physiopathology
Dendrites / pathology
Ion Channel Gating
Mice, Inbred BALB C
Mice, Neurologic Mutants
Molecular Sequence Data
Motor Activity
Point Mutation / genetics*
Purkinje Cells / pathology*
TRPC Cation Channels / chemistry,  genetics*
Grant Support
084655//Wellcome Trust; G0500288//Medical Research Council; MC_U137761449//Medical Research Council; MC_U142684172//Medical Research Council; MC_U142684173//Medical Research Council; MC_U142684175//Medical Research Council; //Medical Research Council
Reg. No./Substance:
0/TRPC Cation Channels; 0/TRPC3 cation channel

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