Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0026850 (muscular dystrophy)
 5,870 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We recently reported that the dystrophin-associated glycoprotein (DAG) complex is biochemically divided into two subcomplexes: one is the dystroglycan complex comprised of 156DAG and 43DAG and the other is the sarcoglycan complex comprised of 50DAG, A3b, and 35DAG. A3b is a novel dystrophin-associated glycoprotein with an approximate molecular mass of 43 kd but is distinct from 43DAG. In the present study, we examined the striated muscles of the dystrophic hamster with anti-A3b antibody in addition to anti-50DAG, anti-43DAG, anti-35DAG, anti-dystrophin, and anti-laminin antibodies by both immunohistochemistry and immunoblot analysis and found that 50DAG, A3b, and 35DAG are selectively lost. This selective defect of the sarcoglycan complex in dystrophic hamster muscles may give rise to dystrophic changes in striated muscles. Thus, the differentiation of the dystrophin-associated glycoprotein complex into the dystroglycan and sarcoglycan complexes is important not only from a biochemical standpoint but also in understanding the cause of muscular dystrophy in the hamster. Our findings further show that the dystrophic hamster may serve as an animal model for a human disease, severe childhood autosomal recessive muscular dystrophy, which has recently been shown to result from a selective defect in the sarcoglycan complex.
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PMID:Sarcoglycan complex is selectively lost in dystrophic hamster muscle. 785 62

To determine if dystrophin and dystrophin-associated glycoproteins (DAGs) are involved in muscle fiber necrosis in the dystrophic hamster, we examined NSJ-my/my (homozygous dystrophic) hamsters introduced from the BIO14.6 strain, by immunohistochemical and immunoblotting methods. Antibodies against dystrophin, utrophin and DAGs including 50DAG (A2), 43DAG (A3a) and 35DAG (A4) were employed for the examination. Dystrophin was stained strongly and utrophin stained very faintly along the sarcolemma of the dystrophic hamster, similar to the control. On the other hand, in the dystrophic hamster 50DAG (A2) and 35DAG (A4) were selectively defective, and 43DAG (A3a) was also decreased, although to a lesser degree. Since these results were almost identical to those seen in severe childhood autosomal recessive muscular dystrophy (SCARMD), the dystrophic hamster appears to be an animal model of SCARMD in which defects in DAGs may result in muscle fiber necrosis despite normal dystrophin expression.
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PMID:Selective defect in dystrophin-associated glycoproteins 50DAG (A2) and 35DAG (A4) in the dystrophic hamster: an animal model for severe childhood autosomal recessive muscular dystrophy (SCARMD). 817 51

Dystrophin is associated with several novel sarcolemmal proteins via the cysteine-rich/C-terminal domains. The dystrophin-associated proteins are classified into three groups: (1) alpha- and beta-dystroglycan, (2) adhalin, 35DAG and A3b, and (3) members of the syntrophin family. Dystrophin interacts with F-actin via the N-terminal domain. Alpha-dystroglycan binds laminin-2, a major component of the basal lamina. These findings indicate that the dystrophin-glycoprotein complex (DGC) links the subsarcolemmal cytoskeleton with the basal lamina, thus providing mechanical stability to the sarcolemmal. The DGC may also play a role in signal transduction. We have reported previously the deficiency of adhalin in skeletal muscle of Arab patients afflicted with severe childhood autosomal recessive muscular dystrophy (SCARMD). SCARMD is now known to affect other races including Europeans and Japanese. Although the phenotype of this disease can mimic Duchenne muscular dystrophy in severe cases, it is sometimes quite mild. SCARMD is genetically heterogeneous. Recently, adhalin gene mutations have been demonstrated in European, Arab and Japanese families with SCARMD. Another locus is on chromosome 13q, however, the mutated gene remains elusive. In the advanced stages of SCARMD, the expression of laminin is disturbed, suggesting that adhalin deficiency may cause the dysfunction of the DGC as a laminin receptor, which may eventually lead to muscle cell death.
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PMID:[Severe childhood autosomal recessive muscular dystrophy]. 875 17