Nature Genetics
10, 301 - 306 (1995)
doi:10.1038/ng0795-301
The mouse dystonia musculorum gene is a neural isoform of bullous pemphigoid antigen 1Arthur Brown1, 2, 4, Gilbert Bernier1, Martine Mathieu1, Janet Rossant2
& Rashmi Kothary1, 3
1Institut du cancer de Montréal, Centre de Recherche L.-C. Simard, Montréal, Québec, Canada H2L 4M1
2Samuel Lunenfeld Research Institute, Mount Sinai Hospital, 600 University Avenue, Toronto, Ontario, Canada M5G 1X5 and Department of Molecular and Medical Genetics, University of Toronto, Canada
3Department of Medicine, University of Montréal, Canada
4Present address: Neurobiology Laboratory, The Salk Institute, 10010 North Torrey Pines Road, La Jolla, California 92037, USA Correspondence should be addressed to R.K.
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 (bpagl). 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.
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