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Homeosis and intestinal tumours in Cdx2 mutant mice

机译:Cdx2突变小鼠的顺势疗法和肠道肿瘤

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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.
机译:在果蝇中,干扰同源异型盒基因尾部的表达会严重破坏人体分割和整体人体模式。果蝇尾有三个小鼠同源物:Cdx1(参考文献2),Cdx2(参考文献3)和Cdx4(参考文献4)。我们已经通过同源重组产生了鼠Cdx2的无效突变。 Cdx2纯合子无效突变体在死后3.5至5.5天之间死亡(d.p.c.)。 Cdx2杂合子突变体表现出可变的表型,其中许多显示出尾巴异常或发育不良。骨骼分析显示椎骨顺势移位,肋骨相容畸形。在生命的头三个月内,Cdx2杂合子中有90%会形成多条肠腺瘤性息肉,尤其是在近端结肠。这些息肉有时包含真正的化生区域。与周围的肠上皮相比,肿瘤细胞不表达其余等位基因中的Cdx2。这些结果表明,Cdx2突变是某些肠道肿瘤发生的主要事件。

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