HOMEOTIC TRANSFORMATIONS AND LIMB DEFECTS IN HOX-A11 MUTANT MICE
HOMEOTIC TRANSFORMATIONS AND LIMB DEFECTS IN HOX-A11 MUTANT MICE
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DOI：
10.1101/gad.7.12a.2318
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发表时间：
1993-12-01
影响因子：
10.5
通讯作者：
POTTER, SS
中科院分区：
文献类型：
--
作者：
SMALL, KM;POTTER, SS
Hox A11是脊椎动物同源异型盒（homeo box，Hox）基因的扩展集合之一，与果蝇同源异型基因Abdominal-B（Abd-B）具有相似性。这些Abd-B型Hox基因已被证明是在最尾部地区的发展中的脊椎动物胚胎和重叠领域内的发展四肢，表明这些基因在模式的形成中起着重要的作用，在approximular和轴向地区的机构。在这份报告中，在小鼠胚胎中的整装原位杂交给出了一个精确的描述Hox A11基因的表达在发展中的肢体和轴域的发展机构。此外，我们在Hox A11中产生了靶向突变，并表征了所得表型，从而开始剖析Hox基因Abd-B亚家族的发育功能。Hox A11突变小鼠表现出双重同源异型转化，第十三胸段后移形成额外的第一腰椎，骶骨区前移，产生另一个腰椎段。此外，在前肢和后肢均观察到骨骼畸形。在变异前肢中，尺骨和桡骨畸形，豌豆骨和三角腕骨融合，籽骨发育异常。在突变的后肢胫骨和腓骨连接不正确，在其远端畸形。此外，胫骨腹侧有一个增大的籽骨。杂合子和纯合子小鼠均显示突变表型，为Hox密码假说增加了额外的复杂性。
Hox A11 is one of the expanded set of vertebrate homeo box (Hox) genes with similarities to the Drosophila homeotic gene, Abdominal-B (Abd-B). These Abd-B-type Hox genes have been shown to be expressed in the most caudal regions of the developing vertebrate embryo and in overlapping domains within the developing limbs, suggesting that these genes play important roles in pattern formation in both appendicular and axial regions of the body. In this report whole-mount in situ hybridization in mouse embryos gave a precise description of Hox A11 gene expression in the developing limbs and in the axial domain of the developing body. In addition, we generated a targeted mutation in Hox A11 and characterized the resulting phenotype to begin to dissect developmental functions of the Abd-B subfamily of Hox genes. Hox A11 mutant mice exhibited double homeotic transformations, with the thirteenth thoracic segment posteriorized to form an additional first lumbar vertebra and with the sacral region anteriorized, generating yet another lumbar segment. Furthermore, skeletal malformations were observed in both forelimbs and hindlimbs. In mutant forelimbs, the ulna and radius were misshapen, the pisiform and triangular carpal bones were fused, and abnormal sesamoid bone development occurred. In mutant hindlimbs the tibia and fibula were joined incorrectly and malformed at their distal ends. Also, an enlarged sesamoid developed ventral to the tibiale bone. Both heterozygous and homozygous mice displayed mutant phenotypes adding an additional level of complexity to the Hox code hypothesis.