Hoxb13 mutations cause overgrowth of caudal spinal cord and tail vertebrae
Hoxb13 mutations cause overgrowth of caudal spinal cord and tail vertebrae
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DOI：
10.1016/s0012-1606(02)00137-9
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发表时间：
2003-04-15
影响因子：
2.7
通讯作者：
Capecchi, MR
中科院分区：
文献类型：
--
作者：
Economides, KD;Zeltser, L;Capecchi, MR
为了解决Hoxb 13（HoxB簇中最5'端的Hox基因）的表达和功能，我们产生了具有该基因的功能丧失和β-半乳糖苷酶报告基因插入等位基因的小鼠。Hoxb 13功能缺失突变纯合子小鼠的尾芽所有主要结构都过度生长，包括发育中的次级神经管（SNT）、尾脊神经节和尾椎骨。使用β-半乳糖苷酶报告基因Hoxb 13，也是一个功能丧失的等位基因，我们发现，Hoxb 13在发育中的脊髓和尾中胚层的表达模式与过度生长表型在纯合突变动物的尾巴密切相关。这些表型可以通过观察到的纯合突变小鼠尾部细胞增殖增加和凋亡水平降低来解释。Hoxb 13功能的分析表明，该5' Hox基因可能作为神经元细胞增殖的抑制剂，SNT中凋亡途径的激活剂，以及尾椎中生长的一般抑制剂。(C)2003 Elsevier Science（美国）。All rights reserved.
To address the expression and function of Hoxb13, the 5' most Hox gene in the HoxB cluster, we have generated mice with loss-of-function and beta-galactosidase reporter insertion alleles of this gene. Mice homozygous for Hoxb13 loss-of-function mutations show overgrowth in all major structures derived from the tail bud, including the developing secondary neural tube (SNT), the caudal spinal ganglia, and the caudal vertebrae. Using the beta-galactosidase reporter allele of Hoxb13, also a loss-of-function allele, we found that the expression patterns of Hoxb13 in the developing spinal cord and caudal mesoderm are closely associated with overgrowth phenotypes in the tails of homozygous mutant animals. These phenotypes can be explained by the observed increased cell proliferation and decreased levels of apoptosis within the tail of homozygous mutant mice. This analysis of Hoxb13 function suggests that this 5' Hox gene may act as an inhibitor of neuronal cell proliferation, an activator of apoptotic pathways in the SNT, and as a general repressor of growth in the caudal vertebrae. (C) 2003 Elsevier Science (USA). All rights reserved.