The mouse Hoxd13spdh mutation, a polyalanine expansion similar to human type II synpolydactyly (SPD), disrupts the function but not the expression of other Hoxd genes
The mouse Hoxd13spdh mutation, a polyalanine expansion similar to human type II synpolydactyly (SPD), disrupts the function but not the expression of other Hoxd genes
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DOI：
10.1006/dbio.2001.0382
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发表时间：
2001-09-15
影响因子：
2.7
通讯作者：
Duboule, D
中科院分区：
文献类型：
--
作者：
Bruneau, S;Johnson, KR;Duboule, D
人类HOXD13基因中的聚丙氨酸扩增可诱导先天性多指畸形（SPD），一种遗传性先天性肢体畸形。分离的小鼠模型显示，由于小鼠基因中相应位置的21 bp重复，丙氨酸自发扩增。这种突变（合多指同源，spdh），当纯合时，在小鼠中引起的畸形与在受影响的人类患者中看到的相似。我们研究了这种情况的遗传学，通过使用几个工程的Hox等位基因，以及通过观察Hox和其他标记基因的表达。我们发现突变的SPDH蛋白诱导了一种功能获得表型，可能是通过表现为比其他Hox基因显性的负性。然而，这种突变似乎独立于Hoxa13起作用，除了HOXD13蛋白本身的轻微减少外，似乎不影响Hox基因的表达。发育研究表明，形态学上的影响主要是由于骨元件生长和骨化的严重迟缓，与后部Hoxd基因功能的普遍损伤一致。(C) 2001学术出版社。
Polyalanine expansion in the human HOXD13 gene induces synpolydactyly (SPD), an inherited congenital limb malformation. A mouse model was isolated, which showed a spontaneous alanine expansion due to a 21-bp duplication at the corresponding place in the mouse gene. This mutation (synpolydactyly homolog, spdh), when homozygous, causes malformations in mice similar to those seen in affected human patients. We have studied the genetics of this condition, by using several engineered Hoxd alleles, as well as by looking at the expression of Hox and other marker genes. We show that the mutated SPDH protein induces a gain-of-function phenotype, likely by behaving as a dominant negative over other Hox genes. The mutation, however, seems to act independently from Hoxa13 and doesn't appear to affect Hox gene expression, except for a slight reduction of the HOXD13 protein itself. Developmental studies indicate that the morphological effect is mostly due to a severe retardation in the growth and ossification of the bony elements, in agreement with a general impairment in the function of posterior Hoxd genes. (C) 2001 Academic Press.