Rapid colorectal adenoma formation initiated by conditional targeting of the APC gene
Rapid colorectal adenoma formation initiated by conditional targeting of the APC gene
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DOI：
10.1126/science.278.5335.120
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发表时间：
1997-10-03
期刊：
影响因子：
56.9
通讯作者：
Noda, H
中科院分区：
文献类型：
--
作者：
Shibata, H;Toyama, K;Noda, H
家族性腺瘤性结肠息肉病（FAP）是一种以多发性结直肠腺瘤为特征的疾病，受影响的个体携带APC基因的种系突变。通过使用条件基因靶向系统，建立了FAP小鼠模型，该模型避免了Apc缺陷的胚胎致死性并将Apc失活特异性地引导至结直肠上皮，将loxP位点插入Ape外显子14周围的内含子中，并将所得突变等位基因（Apc（580 S））引入小鼠种系中。Apc 0（580 S）纯合子小鼠是正常的;然而，在用编码Cre重组酶的腺病毒感染结肠直肠区域后，小鼠在4周内发生腺瘤。腺瘤显示Apc外显子14缺失，表明Apc功能丧失是由Cre-loxP介导的重组引起的。
Familial adenomatous polyposis coli (FAP) is a disease characterized by the development of multiple colorectal adenomas, and affected individuals carry germline mutations in the APC gene. With the use of a conditional gene targeting system, a mouse model of FAP was created that circumvents the embryonic lethality of Apc deficiency and directs Apc inactivation specifically to the colorectal epithelium, loxP sites were inserted into the introns around Ape exon 14, and the resultant mutant allele (Apc(580S)) was introduced into the mouse germline. Mice homozygous for Apc0(580S) were normal; however, upon infection of the colorectal region with an adenovirus encoding the Cre recombinase, the mice developed adenomas within 4 weeks, The adenomas showed deletion of Apc exon 14, indicating that the loss of Apc function was caused by Cre-loxP-mediated recombination.