Janssens Barbara, Mohapatra Bhagyalaxmi, Vatta Matteo, Goossens Steven, Vanpoucke Griet, Kools Patrick, Montoye Tony, van Hengel Jolanda, Bowles Neil E, van Roy Frans, Towbin Jeffrey A
Department of Molecular Biomedical Research, Flanders Interuniversity Institute for Biotechnology, Ghent University, Belgium.
Hum Genet. 2003 Mar;112(3):227-36. doi: 10.1007/s00439-002-0857-5. Epub 2002 Dec 5.
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.
α连环蛋白是α连环蛋白家族的一个新成员，在心肌细胞和睾丸的肾小管周围肌样细胞中表达最为丰富，表明α连环蛋白在特定肌肉组织中具有特定功能。与其他α连环蛋白一样，α连环蛋白在基于钙黏蛋白的细胞间黏附复合体和细胞骨架之间提供了不可或缺的联系，以介导细胞间黏附。通过分离基因组克隆，并结合数据库序列分析，我们已经能够确定分别编码人和小鼠α连环蛋白的CTNNA3和Ctnna3基因的结构。外显子-外显子边界的位置在CTNNA3、Ctnna3以及编码αN-连环蛋白的CTNNA2基因中完全保守。它们与分别编码αE-连环蛋白和α-钙调蛋白的CTNNA1和CTNNAL1基因的边界在很大程度上重叠。这强调了这些α连环蛋白基因是从同一个祖先基因进化而来的。然而，与其他CTNNA基因的内含子相比，CTNNA3和Ctnna3的内含子非常大（通常超过100 kb）。通过荧光原位杂交和基于聚合酶链反应的杂交定位，CTNNA3基因被定位到染色体10q21带。该区域编码一种常染色体显性家族性扩张型心肌病（DCM）的基因，DCM是发病和死亡的常见原因。由于α连环蛋白在健康心脏组织中高度表达，我们将CTNNA3视为一个与10q21-q23位点连锁的DCM家族中的候选疾病基因。然而，对这个家族中CTNNA3基因的所有18个外显子进行突变筛查，并未检测到任何与DCM相关的CTNNA3突变。
