Absence of γ‐sarcoglycan (35 DAG) in autosomal recessive muscular dystrophy linked to chromosome 13q12

Abstract

We have partially sequenced rabbit skeletal muscle T-sarcoglycan an integral component of the dystrophin-glycoprotein complex. Specific antibodies were produced against a 7-sarcoglycan peptide and used to examine the expression of T-sarcoglycan in skeletal muscle of patients with severe childhood autosomal muscular dystrophy linked to chromosome 13q12 (SCARMD). We show by immunofluorescence and Western blotting that in skeletal muscle from these patients T-sarcoglycan is completely absent and c~-and ~-sarcoglycan are greatly reduced in abundance, whereas other components of the DGC are preserved. In addition, we show that in normal muscle ~-, ~-, and T-sarcoglycan constitute a tightly associated sarcolemma complex which can not be disrupted by SDS treatment.

Characterization of δ-Sarcoglycan, a Novel Component of the Oligomeric Sarcoglycan Complex Involved in Limb-Girdle Muscular Dystrophy

“…Peptide Sequencing and Isolation of Human ␦-Sarcoglycan cDNA-Peptides of the 35-kDa component of purified rabbit skeletal muscle DGC were obtained as described previously (24). These peptide sequences were used to search the data base of expressed sequence tags (dbEST) using the TBLASTN search program at the National Center for Biotechnology Information.…”

“…Monoclonal antibodies VIA4 2 against dystrophin and IVD3 1 against ␣-sarcoglycan were previously characterized (2). Affinity-purified rabbit 172 antibody against ␤-sarcoglycan and affinity-purified sheep 0025 antibody against ␥-sarcoglycan were previously characterized (21,24). Monoclonal antibody against the human laminin (MAB1922) ␣2 chain was purchased from Chemicon.…”

“…This synthetic peptide was conjugated with the N-terminal cysteine of keyhole limpet hemocyanin (Pierce) using m-maleimidobenzoic acid-Nhydroxysuccinimide ester (Pierce), mixed with Freund's adjuvant (Sigma) and injected into sheep 0074. Polyclonal antibodies against the peptide were affinity purified from crude sera using BSA-conjugated peptide as described previously (24).…”

“…Recent experiments have demonstrated the existence of two complexes within the DGC (24,25): the dystroglycan complex, composed of ␣-and ␤-dystroglycan, and the sarcoglycan complex, consisting of ␣-, ␤-, and ␥-sarcoglycan.…”

Quel avenir pour la dystrophine ?

“…Dès 1987, date de sa découverte [1], et durant environ 2 décennies la dystrophine voyait presque chaque année autour d'elle apparaître de nouveaux partenaires aussi bien ancrés dans la membrane musculaire que distribués dans le cytoplasme environnant et formant ainsi un large complexe macromoléculaire [2][3][4][5][6][7][8][9][10][11][12][13][14][15][16][17][18][19][20][21]. On va ainsi identifier une protéine apparentée à la dystrophine comme la dystrobrévine avec 2 versions différentes (α et β) et 7 à 8 isoformes respectivement.…”