HEART VALVULOGENESIS--TWO NEW GENES

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We have constructed cDNA libraries of mouse aortic and pulmonic, or semilunar valve (SV) anlage at critical junctures in their development. Subtraction hybridization of these libraries has resulted in the identification of two new genes which are expressed in the SV at murine embryonic day 15. We hypothesize that (1) Xsvr, a new gene with almost complete DNA sequence identity to a STS mapped to the X chromosome, is relevant and possibly critical to normal cardiovascular morphogenesis; and (2) Svnc, a new gene with a Pax-like pattern of expression, mediates cardiac morphogenesis. Our Specific Aims are to: (1) study the developmental expression patterns of these two new genes via in situ hybridization of mouse embryos; (2) obtain full length cDNA and genomic clones of these new genes to study their structures; and (3) to use single stranded conformational polymorphisms (SSCP) and heteroduplex formation to screen patients with X-linked congenital cardiovascular malformations for mutations in Xsvr. Svnc is also likely to be important given its Pax-like expression and the known association of many PAX genes to human disease. We will study it in the mouse in the first two Specific Aims.