HEART VALVULOGENESIS--TWO NEW GENES

我们构建了小鼠主动脉和肺动脉的cDNA文库， 半月瓣（SV）原基在其发展的关键交界处。 这些文库的消减杂交导致了 鉴定了两个在小鼠SV中表达的新基因， 胚胎第15天。 我们假设：（1）Xsvr，一个新的基因， 与映射到X染色体的STS的完整DNA序列同一性， 与正常心血管形态发生相关且可能至关重要; （2）Svnc是一个新基因，具有Pax样表达模式，介导 心脏形态发生我们的具体目标是：（1）研究 这两个新基因的发育表达模式，通过原位 小鼠胚胎杂交;（2）获得全长cDNA和基因组 克隆这些新基因，研究它们的结构;（3）使用 单链构象多态性（SSCP）和异源双链 筛查X连锁先天性心血管疾病患者 Xsvr突变的畸形。svnc也可能很重要 考虑到它的Pax样表达和已知的许多PAX基因的关联， 人类疾病。 我们将在前两个实验中对小鼠进行研究 具体目标。

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.