Disease relevance of SSPN

• Although we identified three intragenic polymorphisms, we did not find any cases of muscular dystrophy associated with primary mutations in the sarcospan gene [1].
• Finally, we have identified an important case of limb girdle muscular dystrophy and cardiomyopathy with normal expression of sarcospan [1].
• We also show that sarcospan expression is dramatically reduced in muscle from patients with Duchenne muscular dystrophy [2].
• The gene encoding sarcospan maps to human chromosome 12p11.2, which falls within the genetic locus for congenital fibrosis of the extraocular muscle, an autosomal dominant muscular dystrophy [2].
• Recombinant alpha-sarcoglycan adenovirus injection into Sgca-deficient muscles restored the sarcoglycan complex and sarcospan to the membrane [3].
• Sarcospan transgenic muscle does not display sarcolemma damage, which is distinct from dystrophin- and sarcoglycan-deficient muscular dystrophies [4].

High impact information on SSPN

• Molecular analysis of Sgca-null mice demonstrated that the absence of alpha-sarcoglycan resulted in the complete loss of the sarcoglycan complex, sarcospan, and a disruption of alpha-dystroglycan association with membranes [3].
• In particular, sarcospan was absent in a gamma-sarcoglycanopathy patient with normal levels of alpha-, beta- and delta-sarcoglycan [1].
• Based on our findings that sarcospan is integrally associated with the sarcoglycans, we screened >50 autosomal recessive muscular dystrophy cases for mutations in sarcospan [1].
• We show that sarcospan, a novel tetraspan-like protein, is also lost in patients with either a complete or partial loss of the sarcoglycans [1].
• Immunohistochemical and immunoblot analyses of BSG(-)(/-)mice demonstrated that deficiency of beta-sarcoglycan also caused loss of all of the other sarcoglycans as well as of sarcospan in the sarcolemma [5].

Biological context of SSPN

• Sarcospan is a member of the dystrophin associated protein complex in skeletal and extraocular muscle and maps to human chromosome 12p11 [6].
• Finally, sarcospan was electronically mapped to bacterial artificial chromosomes that are considered to be outside of the CFEOM1 critical region [6].
• Identification of a PCR-based restriction fragment length polymorphism confirmed biallelic expression of KRAG but suggested allele-specific splicing differences in tumors [7].
• A potential human homologue, EST05985, was identified and provisionally mapped to human chromosome 12, a chromosome syntenic to mouse chromosome 6, the previously mapped location of KRAG [8].
• The gene, designated KRAG (Ki-ras-associated gene) has a CG-rich first exon and promoter region and a long 3' untranslated region and encodes 216 amino acids [8].

Anatomical context of SSPN

• By RNA analysis, we observed expression of alpha-, beta-, gamma-, delta-, epsilon-SG, and SSPN in smooth muscle cells [9].
• In endothelial cells, immunostaining only evidenced the presence of epsilon-SG and SSPN [9].
• The distribution of dystrophin-associated proteins (beta-dystroglycan, alpha-, beta-, gamma- and delta-sarcoglycan, alpha-syntrophin and sarcospan) were studied in obliquely striated muscle of the leech Pontobdella muricata [10].
• The remaining antigens, A15, CoO29, KRAG, L6, TI-1 and il-TMP, are expressed at low levels in very few cell lines without any specific pattern [11].
• Sarcospan is only absent from sciatic nerve structures [12].

Other interactions of SSPN

• Sequencing of the sarcospan gene in CFEOM1 patients from 6 families revealed no mutations [6].
• Analysis of a region of DNA, coamplified in tumors with KRAS2, resulted in the identification of the human homologue of the mouse KRAG gene [7].

Analytical, diagnostic and therapeutic context of SSPN

• A human KRAG cDNA sequence, with a structure similar to that encoded by the amplified gene in mouse Y1 adrenal carcinoma cells, was isolated by RT-PCR [7].
• Using this antibody we investigated the localization of sarcospan and its spacial relation to the components of sarcoglycan subcomplex in normal human skeletal myofibers by immunofluorescent microscopy and immunogold electron microscopy [13].

References