Targeted mutations in Hoxa-9 and Hoxb-9 reveal synergistic interactions
Targeted mutations in Hoxa-9 and Hoxb-9 reveal synergistic interactions
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DOI：
10.1006/dbio.1996.8440
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发表时间：
1997-01-15
影响因子：
2.7
通讯作者：
Capecchi, MR
中科院分区：
文献类型：
--
作者：
Chen, F;Capecchi, MR
小鼠是用含有同源框的基因hoxb-9的靶向破坏产生的。这种突变的纯合子小鼠在第一和第二肋骨的发育中表现出缺陷。在大多数情况下，第一和第二肋骨在第一和第二对肋骨通常附接到胸骨的点附近融合。胸骨外展伴随肋骨融合。这些包括肋骨与胸骨的异常附着、胸骨肋间节段数量的减少以及肋间节段的异常生长。超过一半的纯合子突变体，以及一些杂合子，也有第八肋骨连接到胸骨。这些结果表明hoxb-9在胸部骨骼元素的特化中起重要作用。为了揭示旁系同源Hox基因hoxa-9和hoxb-9之间的潜在相互作用，将两种突变的杂合子小鼠杂交。两种突变的纯合子小鼠表现出比通过添加单个突变表型预测的更严重的表型。肋骨和胸骨缺陷的表达率和表达率都增加，表明这些基因之间存在协同作用。特别是胸骨缺损会大大加重。有趣的是，hoxb-9和hoxa-9/ hoxb-9突变小鼠的缺陷集中在沿着脊柱的椎体类型之间的过渡点。(C)北京：科学出版社.
Mice were generated with a targeted disruption of the homeobox-containing gene hoxb-9. Mice homozygous for this mutation show defects in the development of the first and second ribs. In most cases the first and second ribs are fused near the point at which the first and second pairs of ribs normally attach to the sternum. Abnormalities of the sternum accompany the rib fusions. These include abnormal attachment of the ribs to the sternum, a reduction in the number of intercostal segments of the sternum, and abnormal growth of the intercostal segments. Over half of the homozygous mutants, as well as some heterozygotes, also have an eighth rib attached to the sternum. These results show that hoxb-9 plays a significant role in the specification of thoracic skeletal elements. To reveal potential interactions between the paralogous Hox genes hoxa-9 and hoxb-9 mice heterozygous for both mutations were intercrossed. Mice homozygous for both mutations show more severe phenotypes than predicted by the addition of the individual mutant phenotypes. Both the penetrance and the expressivity of the rib and sternal defects are increased, suggesting synergistic interactions between these genes. In particular, the sternum defects are greatly exacerbated. Interestingly, the defects in hoxb-9 and hoxa-9/ hoxb-9 mutant mice are concentrated along the axial column at points of transition between vertebral types. (C) 1997 Academic Press.