CHROMOSOMAL LOCALIZATION, GENOMIC ORGANIZATION, AND DEVELOPMENTAL EXPRESSION OF THE MURINE CAVEOLIN GENE FAMILY (CAV-1, CAV-2, AND CAV-3) -CAV-1 AND CAV-2 GENES MAP TO A KNOWN TUMOR SUPPRESSOR LOCUS (6-A2 731)/

Careolins (Cav-1, -2, and -3) are a gene family of cytoplasmic membran e-anchored scaffolding proteins that: (i) help to sculpt caveolae memb ranes from the plasma membrane proper; and (ii) participate in the seq uestration of inactive signaling molecules, In the adult, caveolin-1 a nd -2 are coexpressed and are most abundant in type I pneumocytes, end othelia, fibroblastic cells and adipocytes, while the expression of ca veolin-3 is restricted to striated muscle cells, However, little is kn own regarding the genomic organization and developmental expression of the caveolin gene family. Here, using the mouse as a model system, we examine the chromosomal localization, the detailed intron-exon organi zation, and developmental expression pattern of the caveolin gene fami ly, cDNAs encoding caveolin-1, -2, and -3 were used as probes to isola te murine genomic clones containing these genes, Fluorescence in situ hybridization (FISH) analysis using these genomic clones as probes rev eals that all three caveolin genes are localized to murine chromosome 6, Specifically, caveolin-1 and -2 co-localize to chromosomal region 6 -A2, while caveolin-3 is located within the chromosomal region 6-E1, S earches of the NCBI Human/Mouse Homology map indicate that murine regi on 6-A2 corresponds to human chromosome 7q31. As this region (6-A2/7q3 1) is the site of an as Set unidentified tumor suppressor gene(s), our mapping studies clearly define caveolin-1 and caveolin-2 as candidate genes that may de deleted at these loci. All three caveolin genes sho w similar intron-exon organization, with the last exon of each gene en coding the bulk of the known caveolin functional domains. The boundary position of the last exon is essentially identical in all three caveo lin genes, suggesting that they may have arisen through gene duplicati on events, Developmentally, all three caveolins were expressed late du ring mouse embryogenesis as assessed by Northern and Western blot anal ysis. We examined the localization of the caveolin proteins in Section s of da 16 mouse embryos using a well-characterized panel of antibody probes, Caveolin-1 and -2 were most abundantly expressed in the develo ping lung parenchyma, while caveolin-3 was most abundantly expressed i n developing tissues that consist primarily of skeletal muscle cells. ris the expression of all three caveolins in the adult is highest in t erminally differentiated cell types, this is consistent with the idea that caveolins may be viewed as late markers of differentiation during embryogenesis. (C) 1998 Federation of European Biochemical Societies.