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.
Subject(s)
Autoantigens/genetics , Carrier Proteins , Collagen , Cytoskeletal Proteins/genetics , Dystonia Musculorum Deformans/genetics , Nerve Tissue Proteins/genetics , Non-Fibrillar Collagens , Pemphigoid, Bullous/immunology , Amino Acid Sequence , Animals , Base Sequence , DNA, Complementary/genetics , Dystonia Musculorum Deformans/immunology , Dystonin , Gene Expression , Humans , In Situ Hybridization , Mice , Mice, Transgenic , Molecular Sequence Data , Mutation , Pemphigoid, Bullous/genetics , Sequence Homology, Amino Acid , Species Specificity , Transcription, Genetic , Collagen Type XVIIABSTRACT
In 37 patients with some hereditary diseases of the nervous system (deforming muscular dystonia, hepatocerebral dystrophy, essential tremor, etc.), as well as in 22 healthy subjects (donors), the percentage and the absolute content of the T- and B-lymphocytes in the blood were determined. Use was made of the reactions of spontaneous, active, and complementary rosette formation and determination of the B-cells from superficial immunoglobulins. In all the hereditary diseases listed a drop of the content of thymus-dependent lymphocytes and an increase of the capacity of lymphocytes for complementary rosette formation were revealed. The data obtained can be, probably, interpreted as evidences of a secondary immunodeficient state, possibly, caused by metabolic disturbances which are known to play an essential role in the pathogenesis of hereditary diseases of the nervous system.
Subject(s)
B-Lymphocytes/immunology , Nervous System Diseases/genetics , T-Lymphocytes/immunology , Adult , Animals , Antibodies , Complement System Proteins , Dystonia Musculorum Deformans/immunology , Erythrocytes/immunology , Female , Hepatolenticular Degeneration/immunology , Humans , Male , Middle Aged , Nervous System Diseases/immunology , Receptors, Antigen, B-Cell/analysis , Sheep/immunology , Tremor/geneticsABSTRACT
Results of examining the sera of 11 normal donors and 37 patients with various neutogenetic diseases using, the Coons indirect immunofluorescence technique are presented. The patients' immunoglobulins could be better fixed on nervous tissue components than those of the control donors. This seems likely to be due to both a rise in the content of serum immunoglobulins and accumulation of specific anticerebral antibodies in the patients' blood. It is suggested that in all cases of using indirect immunofluorescence the quantitative determination of immunoglobulins and serum titration should be carried out.
