title: Assessment of the CTNNA3 gene encoding human alpha T-catenin regarding its involvement in dilated cardiomyopathy.
abstract: Alpha T-catenin is a novel member of the alpha-catenin family, which shows most abundant expression in cardiomyocytes and in peritubular myoid cells of the testis, pointing to a specific function for alpha T-catenin in particular muscle tissues. Like other alpha-catenins, alpha T-catenin provides an indispensable link between the cadherin-based cell-cell adhesion complex and the cytoskeleton, to mediate cell-cell adhesion. By isolating genomic clones, combined with database sequence analysis, we have been able to determine the structure of the CTNNA3 and Ctnna3 genes, encoding human and mouse alpha T-catenin, respectively. The positions of the exon-exon boundaries are completely conserved in CTNNA3, Ctnna3, and the alpha N-catenin encoding CTNNA2 gene. They overlap largely with the boundaries of the CTNNA1 and CTNNAL1 genes encoding alpha E-catenin and alpha-catulin, respectively. This emphasizes that these alpha-catenin genes evolved from the same ancestor gene. Nevertheless, the introns of CTNNA3 and Ctnna3 are remarkably large (often more than 100 kb) compared with introns of other CTNNA genes. The CTNNA3 gene was mapped to chromosome band 10q21 by both fluorescence in situ hybridization and polymerase-chain-reaction-based hybrid mapping. This region encodes a gene for autosomal dominant familial dilated cardiomyopathy (DCM), a common cause of morbidity and mortality. As alpha T-catenin is highly expressed in healthy heart tissue, we have considered CTNNA3 as a candidate disease gene in a family showing DCM linkage to the 10q21-q23 locus. Mutation screening of all 18 exons of the CTNNA3 gene in this family has, however, not detected any DCM-linked CTNNA3 mutations.
authors.affiliation: Department of Molecular Biomedical Research, Flanders Interuniversity Institute for Biotechnology, Ghent University, Belgium.
authors.forename: Barbara
authors.initials: B
authors.lastname: Janssens
authors.forename: Bhagyalaxmi
authors.initials: B
authors.lastname: Mohapatra
authors.forename: Matteo
authors.initials: M
authors.lastname: Vatta
authors.forename: Steven
authors.initials: S
authors.lastname: Goossens
authors.forename: Griet
authors.initials: G
authors.lastname: Vanpoucke
authors.forename: Patrick
authors.initials: P
authors.lastname: Kools
authors.forename: Tony
authors.initials: T
authors.lastname: Montoye
authors.forename: Jolanda
authors.initials: J
authors.lastname: van Hengel
authors.forename: Neil E
authors.initials: NE
authors.lastname: Bowles
authors.forename: Frans
authors.initials: F
authors.lastname: van Roy
authors.forename: Jeffrey A
authors.initials: JA
authors.lastname: Towbin
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D002311:Cardiomyopathy, Dilated / Q000235:genetics*; D002874:Chromosome Mapping; D002879:Chromosomes, Human, Pair 10 / Q000235:genetics*; D003001:Cloning, Molecular; D003598:Cytoskeletal Proteins / Q000235:genetics*; D017931:DNA Primers; D018076:DNA, Complementary / Q000032:analysis*; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D051379:Mice; D008969:Molecular Sequence Data; D016133:Polymerase Chain Reaction; D051178:alpha Catenin / Q000235:genetics*
chemical_list: C495273:CTNNA1 protein, human; C575065:CTNNA3 protein, mouse; C495274:CTNNAL1 protein, human; C495272:Ctnna1 protein, mouse; D003598:Cytoskeletal Proteins; D017931:DNA Primers; D018076:DNA, Complementary; D051178:alpha Catenin