Localization of the human caveolin-3 gene to the D3S18/D3S4163/D3S4539 locus (3p25), in close proximity to the human oxytocin receptor gene - Identification of the caveolin-3 gene as a candidate for deletion in 3p-syndrome

Caveolin-3, a muscle-specific caveolin-related protein, is the principal st ructural protein of caveolae membrane domains in striated muscle cell types (cardiac and skeletal). Recently, we identified an autosomal dominant form of limb girdle muscular dystrophy in humans that is due to mutations withi n exon 2 of the caveolin-3 gene (3p25). However, the detailed location of t he human caveolin-3 gene and its position with regard to neighboring genes remains unknown. Here, we have isolated three independent BAC clones contai ning the human caveolin-3 gene. Using a PCR-based approach, we determined t hat these clones contain both exons 1 and 2 of the human cavealin-3 gene. I n addition, we performed microsatellite marker analysis of these BAC clones , using a panel of 13 markers that are known to map within the 3p25 region. Our results indicate that these BAC clones contain the following three mar kers: D3S18, SHGC-1079 (also known as D3S4163) and D3S4539, Interestingly, D3S18 is a marker for two known human diseases, von Hippel-Lindau disease a nd 3p-syndrome, As D3S4163 and D3S4539 are known to map in the vicinity of the 3' end of the human oxytocin receptor gene, we determined if these cave olin-3 positive BACs also contain the oxytocin receptor gene. We show that (i) these BACs contain all four exons of the oxytocin receptor gene and (ii ) that the genes encoding caveolin-3 and the oxytocin receptor are located similar to 7-10 kb apart and in the opposite orientation. As 3p-syndrome is characterized by cardiac septal defects and caveolin-3 is expressed primar ily in the heart and skeletal muscle, caveolin-3 is a candidate gene that m ay be deleted in 3p-syndrome. (C) 1999 Federation of European Biochemical S ocieties.