POTENTIAL MODEL OF CYSTIC FIBROSIS

我们建议在小鼠基因组中为小鼠类似物创建一个缺失 人类MET癌基因。纯合缺失的小鼠将是 人类疾病囊性纤维化(CF)的可能模型。它有 最近发现的MET，它映射到人类的7号染色体，甚至可能 是CF基因还是与囊性纤维化密切相关(小于0.7 Cm)。由于小鼠之间存在高度连锁性 而人类，辐射诱导的小鼠MET基因的缺失可能很好 还去除了小鼠类似的Cf基因。我们将寻找这样一个 通过筛查亲本之一的F1小鼠的DNA来进行缺失 作为研究三角正在进行的突变项目的一部分进行了辐射 研究所。这是一个高风险项目，因为(1)筛查 受辐射动物的后代将不会有效率，除非我们能够 鉴定亲本之间的限制性片段长度多态性 我们将筛选其F1后代的菌株，(2)后代数量 需要筛查的小鼠很大，(3)Met-“Cf”部分 小鼠基因组可能包括胚胎发育所必需的基因，如 缺失的纯合子不会存活足够长的时间 有用，以及(4)这种联系可能无法维持。尽管如此，我们相信 小鼠模型在治疗方面的巨大价值包括 基因疗法，值得冒这个险。

We propose to create a deletion in the mouse genome for the mouse analogue of the human met oncogene. Mice homozygous for the deletion would be a possible model for the human disorder cystic fibrosis (CF). It has recently been found that met, which maps to human chromosome 7, might even be the CF gene or is very closely linked to cystic fibrosis (less than 0.7 cM). Since there is a high degree of conservation of linkage between mouse and man, a radiation-induced deletion of the met locus in mice may well also remove the mouse analogue of the CF gene. We will search for such a deletion by screening DNA of F1 mice where one of the parents has been irradiated as part of an ongoing mutation project at Research Triangle Institute. This is a high risk project because (1) the screening of progeny from irradiated animals will not be efficient unless we are able to identify a restriction fragment length polymorphism between the parental strains whose F1 progeny we will be screening, (2) the number of progeny mice which will need to be screened is large, (3) the met-"CF" portion of the mouse genome may include genes necessary for embryonic development such that the homozygotes for the deletion would not survive long enough to be useful, and (4) the linkage may not be maintained. Nonetheless, we believe that the immense value of a murine model for treatment efforts, including gene therapy, warrants taking the risk.