HEART VALVULOGENESIS--TWO NEW GENES

我们已经构建了小鼠主动脉和肺组织的cDNA文库，或者 半月瓣(SV)原基在其发育的关键时刻。 这些文库的消减杂交导致了 两个新基因在小鼠SV中表达的鉴定 胚胎第15天。我们假设(1)Xsvr，一个几乎与 与定位于X染色体的STS的完整DNA序列同源性为 与正常的心血管形态发生相关并且可能是关键的； 和(2)Svnc，一种具有类似Pax表达模式的新基因，介导 心脏形态发生。我们的具体目标是：(1)研究 这两个新基因的原位发育性表达谱 小鼠胚胎杂交；(2)获得全长c DNA和基因组 克隆这些新基因以研究它们的结构；以及(3)使用 单链构象多态性(SSCP)与异源双链 X连锁先天心血管病患者的筛查 Xsvr基因突变的畸形。Svnc也可能是重要的 鉴于其类似Pax的表达和许多PAX基因的已知关联 人类疾病。在前两节中，我们将在老鼠身上进行研究 明确的目标。

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.