VERTEBRATE SPROUTY GENES--CANDIDATE FGF INHIBITORS

越来越多的证据表明，成纤维细胞生长因子家族的信号分子 在脊椎动物的许多方面起着核心的调节作用 胚胎发生，也可能在肿瘤的发生中发挥作用。最近，一位 一种名为Sprouty(Spry)的基因，它显然编码成纤维细胞生长因子的一种抑制因子 功能，已在果蝇中被鉴定。我们有 分离并鉴定了两个小鼠基因Spry1和Spry2， 与果蝇Spry(D-spry)关系密切。这些实验 这里描述的是利用转基因小鼠的最新改进 技术来详细研究这两个基因的功能。 同时使用Cre和FLP DNA的先进基因打靶方法 重组酶将用于产生一系列等位基因突变 Spry1和SPRY2基因座，并获得组织特异性敲除 这些基因。将对突变动物进行研究，以 阐明Spry1和SPRY2在发育过程中的特定功能， 并探讨它们作为肿瘤抑制基因的可能功能。 此外，我们描述了使用基因替换策略的实验 探索Spry1和SPRY2基因的唯一性或等价性 功能。

There is increasing evidence that the FGF family of signaling molecules plays a central role in the regulation of many aspects of vertebrate embryogenesis, and may also play a role in tumorigenesis. Recently, a gene called sprouty (spry), which apparently encodes an inhibitor of FGF function, has been identified in Drosophila melanogaster. We have isolated and begun to characterize two mouse genes, Spry1 and Spry2, that are closely related to Drosophila spry (D-spry). The experiments described here take advantage of recent improvements in transgenic mouse technology to study in detail the functions of these two genes. Advanced gene targeting methods employing both Cre and Flp DNA recombinases will be used to produce an allelic series of mutations at the Spry1 and Spry2 loci, and to obtain tissue-specific knock-outs of these genes. Studies of the mutant animals will be performed to elucidate the specific functions of Spry1 and Spry2 during development, and to investigate their possible function as tumor suppressor genes. In addition, we describe experiments using a gene replacement strategy to explore the uniqueness or equivalent of Spry1 and Spry2 gene functions.