Chawengsaksophak K, James R, Hammond V E, Köntgen F, Beck F
Howard Florey Institute of Experimental Physiology and Medicine, University of Melbourne, Parkville, Victoria, Australia.
Nature. 1997 Mar 6;386(6620):84-7. doi: 10.1038/386084a0.
In Drosophila, disturbing the expression of the homeobox gene caudal causes a severe disruption in body segmentation and global body patterning. There are three mouse homologues of Drosophila caudal: Cdx1 (ref. 2), Cdx2 (ref. 3) and Cdx4 (ref. 4). We have generated a null mutation of murine Cdx2 by homologous recombination. Cdx2 homozygote null mutants die between 3.5 and 5.5 days post coitum (d.p.c.). Cdx2 heterozygote mutants exhibit a variable phenotype, with many showing tail abnormalities or stunted growth. Skeletal analysis demonstrates a homeotic shift of vertebrae and compatible malformations of the ribs. Within the first three months of life, 90% of Cdx2 heterozygotes develop multiple intestinal adenomatous polyps, particularly in the proximal colon. These polyps occasionally contain areas of true metaplasia. In contrast to the surrounding intestinal epithelium, the neoplastic cells do not express Cdx2 from the remaining allele. These results suggest that Cdx2 mutation is the primary event in the genesis of some intestinal tumours.
在果蝇中，干扰同源异型框基因尾型（caudal）的表达会导致身体节段和整体身体模式的严重破坏。果蝇尾型基因有三个小鼠同源基因：Cdx1（参考文献2）、Cdx2（参考文献3）和Cdx4（参考文献4）。我们通过同源重组产生了小鼠Cdx2的无效突变。Cdx2纯合子无效突变体在交配后3.5至5.5天死亡。Cdx2杂合子突变体表现出可变的表型，许多表现出尾巴异常或生长发育迟缓。骨骼分析显示椎骨发生同源异型转变以及肋骨出现相应畸形。在出生后的前三个月内，90%的Cdx2杂合子会发展出多个肠道腺瘤性息肉，尤其是在近端结肠。这些息肉偶尔含有真正化生的区域。与周围的肠上皮不同，肿瘤细胞不表达来自剩余等位基因的Cdx2。这些结果表明，Cdx2突变是某些肠道肿瘤发生的主要事件。
