Abstract
Dystonia musculorum (dt) is a hereditary neurodegenerative disease in mice that leads to a sensory ataxia. We describe cloning of a candidate dt gene, dystonin, that is predominantly expressed in the dorsal root ganglia and other sites of neurodegeneration in dt mice. Dystonin encodes an N-terminal actin binding domain and a C-terminal portion comprised of the hemidesmosomal protein, bullous pemphigoid antigen 1 (bpag1). dt and bpag1 are part of the same transcription unit which is partially deleted in a transgenic strain of mice, Tg4, that harbours an insertional mutation at the dt locus, and in mice that carry a spontaneous dt mutation, dtAlb. We also demonstrate abnormal dystonin transcripts in a second dt mutant, dt24J. We conclude that mutations in the dystonin gene are the primary genetic lesion in dt mice.
Publication types
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Comparative Study
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Research Support, Non-U.S. Gov't
MeSH terms
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Amino Acid Sequence
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Animals
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Autoantigens / genetics*
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Base Sequence
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Carrier Proteins*
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Collagen Type XVII
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Collagen*
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Cytoskeletal Proteins / genetics*
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DNA, Complementary / genetics
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Dystonia Musculorum Deformans / genetics*
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Dystonia Musculorum Deformans / immunology
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Dystonin
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Gene Expression
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Humans
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In Situ Hybridization
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Mice
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Mice, Transgenic
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Molecular Sequence Data
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Mutation
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Nerve Tissue Proteins / genetics*
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Non-Fibrillar Collagens*
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Pemphigoid, Bullous / genetics
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Pemphigoid, Bullous / immunology*
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Sequence Homology, Amino Acid
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Species Specificity
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Transcription, Genetic
Substances
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Autoantigens
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Carrier Proteins
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Cytoskeletal Proteins
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DNA, Complementary
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DST protein, human
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Dst protein, mouse
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Dystonin
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Nerve Tissue Proteins
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Non-Fibrillar Collagens
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Collagen
Associated data
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GENBANK/U22452
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GENBANK/U25158