| A point mutation in TRPC3 causes abnormal Purkinje cell development and cerebellar ataxia in moonwalker mice. | |
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MedLine Citation:
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PMID: 19351902 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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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. |
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Authors:
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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:
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Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2009-04-07 |
Journal Detail:
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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:
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Created Date: 2009-05-06 Completed Date: 2009-05-29 Revised Date: 2009-11-18 |
Medline Journal Info:
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Nlm Unique ID: 7505876 Medline TA: Proc Natl Acad Sci U S A Country: United States |
Other Details:
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Languages: eng Pagination: 6706-11 Citation Subset: IM |
Affiliation:
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Medical Research Council Functional Genomics Unit, Department of Physiology, Anatomy and Genetics, University of Oxford, South Parks Road, Oxford OX1 3QX, United Kingdom. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Amino Acid Sequence Animals Cell Differentiation Cerebellar Ataxia / pathology*, physiopathology Dendrites / pathology Ion Channel Gating Male Mice Mice, Inbred BALB C Mice, Neurologic Mutants Molecular Sequence Data Motor Activity Phosphorylation Point Mutation / genetics* Purkinje Cells / pathology* TRPC Cation Channels / chemistry, genetics* |
| Grant Support | |
ID/Acronym/Agency:
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//Medical Research Council |
| Chemical | |
Reg. No./Substance:
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0/TRPC Cation Channels; 0/TRPC3 cation channel |
| Comments/Corrections | |
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