Cre-loxP chromosome engineering of a targeted deletion in the mouse corresponding to the 3p21.3 region of homozygous loss in human tumours
Cre-loxP chromosome engineering of a targeted deletion in the mouse corresponding to the 3p21.3 region of homozygous loss in human tumours
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DOI：
10.1038/sj.onc.1205530
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发表时间：
2002-07-04
期刊：
影响因子：
8
通讯作者：
Rabbitts, PH
中科院分区：
文献类型：
--
作者：
Smith, AJH;Xian, J;Rabbitts, PH
染色体缺失是上皮肿瘤的常见特征，当进一步定义为纯合缺失时，通常是肿瘤抑制基因的位置。3号染色体短臂内的缺失在人类癌症中非常频繁地发生：在肺癌和乳腺癌细胞系中，3p21.3（Luca）区域的最小丢失区域已被定义为重叠纯合缺失。使用Cre-loxP染色体工程的快速策略，在小鼠种系中产生约370 kb的缺失，对应于3p21.3处的缺失区域。纯合子的缺失是胚胎致死的。杂合子发育正常，尽管对于包括候选肿瘤抑制基因Rassf 1在内的12个基因来说是单倍不足的。由于对3p21.3的损伤通常发生在导致恶性肿瘤的遗传变化序列的早期，特别是在肺癌和乳腺癌中，因此对这些小鼠的进一步遗传损伤将提供对这些肿瘤的多步骤肿瘤发生进行建模的机会。
Chromosomal deletions are a common feature of epithelial tumours and when further defined by homozygous deletions, are often the location of tumour suppressor genes. Deletions within the short arm of chromosome 3 occur very frequently in human carcinomas: a minimal region of loss at 3p21.3 (the Luca) region has been defined by overlapping homozygous deletions in lung and breast cancer cell lines. Using a rapid strategy for Cre-loxP chromosome engineering, a deletion of approximately 370 kb was created in the mouse germline corresponding to the deleted region at 3p21.3. The deletion when homozygous is embryonic lethal. Heterozygotes develop normally despite being haplo-insufficient for twelve genes including the candidate tumour suppressor gene Rassf1. Because damage to 3p21.3 often occurs very early in the sequence of genetic changes that lead to malignancy, particularly in lung and breast cancer, further genetic damage to these mice will provide the opportunity to model multi-step tumorigenesis of these tumours.