The mouse dystonia musculorum gene is a neural isoform of bullous pemphigoid antigen 1.
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.
Brown
A
A
Institut du cancer de Montréal, Centre de Recherche L.-C. Simard, Québec, Canada.
Bernier
G
G
Mathieu
M
M
Rossant
J
J
Kothary
R
R
D000595:Amino Acid Sequence; D000818:Animals; D001324:Autoantigens / Q000235:genetics*; D001483:Base Sequence; D002352:Carrier Proteins; D003094:Collagen; D003598:Cytoskeletal Proteins / Q000235:genetics*; D018076:DNA, Complementary / Q000235:genetics; D004422:Dystonia Musculorum Deformans / Q000235:genetics* / Q000276:immunology; D000071821:Dystonin; D015870:Gene Expression; D006801:Humans; D017403:In Situ Hybridization; D051379:Mice; D008822:Mice, Transgenic; D008969:Molecular Sequence Data; D009154:Mutation; D009419:Nerve Tissue Proteins / Q000235:genetics*; D024041:Non-Fibrillar Collagens; D010391:Pemphigoid, Bullous / Q000235:genetics / Q000276:immunology*; D017386:Sequence Homology, Amino Acid; D013045:Species Specificity; D014158:Transcription, Genetic; D000097805:Collagen Type XVII
D001324:Autoantigens; D002352:Carrier Proteins; D003094:Collagen; D003598:Cytoskeletal Proteins; D018076:DNA, Complementary; D000071821:Dystonin; D009419:Nerve Tissue Proteins; D024041:Non-Fibrillar Collagens; D000097805:Collagen Type XVII; C486268:DST protein, human; C095667:Dst protein, mouse