VERTEBRATE SPROUTY GENES--CANDIDATE FGF INHIBITORS

越来越多的证据表明，FGF家族的信号分子 在脊椎动物的许多方面的调节中起着核心作用 胚胎发生，也可能在肿瘤发生中发挥作用。 近日一 一种名为sprougty（spry）的基因，它显然编码FGF抑制剂 功能，已确定在果蝇。 我们有 分离并开始鉴定两个小鼠基因，Spry 1和Spry 2， 与Drosophila spry（D-spry）密切相关。 实验 本文所述的方法利用了转基因小鼠的最新进展， 技术来详细研究这两个基因的功能。 使用Cre和Flp DNA的先进基因打靶方法 重组酶将用于产生等位基因系列突变， Spry 1和Spry 2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， 阐明Spry 1和Spry 2在发育过程中的具体功能， 并研究其作为肿瘤抑制基因的可能功能。 此外，我们描述了使用基因置换策略的实验 探索Spry 1和Spry 2基因的独特性或等同性， 功能协调发展的

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.