A TARGETED CHAIN-TERMINATION MUTATION IN THE MOUSE APC GENE RESULTS IN MULTIPLE INTESTINAL TUMORS
A TARGETED CHAIN-TERMINATION MUTATION IN THE MOUSE APC GENE RESULTS IN MULTIPLE INTESTINAL TUMORS
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DOI：
10.1073/pnas.91.19.8969
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发表时间：
1994-09-13
影响因子：
11.1
通讯作者：
KUCHERLAPATI, R
中科院分区：
文献类型：
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作者：
FODDE, R;EDELMANN, W;KUCHERLAPATI, R
人类腺瘤性结肠息肉病（APC）基因的生殖系突变导致家族性腺瘤性息肉病，这是一种常染色体显性遗传疾病，其特征是大肠中多发性腺瘤性息肉的早期发作，具有发展为结直肠癌的高可能性。为了了解APC在肠道肿瘤形成中的作用，我们在小鼠Apc基因的第15外显子中引入了链终止突变，并利用其通过在胚胎干细胞中同源重组来修饰内源性基因。Apc基因修饰杂合的小鼠以类似于在家族性腺瘤性息肉病患者和携带称为多发性肠肿瘤（Min）的突变的小鼠中观察到的方式逐渐发展肠肿瘤。我们的研究结果表明，Apc基因修饰是一个关键的事件，在启动肠道肿瘤的形成，并导致在常染色体显性倾向于发展自发性结肠和肠道肿瘤的小鼠。
Germ line mutations in the human adenomatous polyposis coli (APC) gene result in familial adenomatous polyposis, an autosomal dominant disorder characterized by the early onset of multiple adenomatous polyps in the large bowel with a high likelihood of developing colorectal carcinomas. To understand the role of APC in intestinal tumor formation, we have introduced a chain-termination mutation in the 15th exon of the mouse Apc gene and employed it to modify the endogenous gene by homologous recombination in embryonic stem cells. Mice which are heterozygous for the Apc gene modification progressively develop intestinal tumors in a manner that is similar to that observed in patients with familial adenomatous polyposis and in mice which carry a mutation called multiple intestinal neoplasia (Min). Our results indicate that the Apc gene modification is a critical event in the initiation of intestinal tumor formation and results in an autosomal dominant predisposition toward development of spontaneous colonic and intestinal tumors in mice.