A MOUSE MODEL OF GREIG CEPHALOPOLYSYNDACTYLY SYNDROME - THE EXTRA-TOES(J) MUTATION CONTAINS AN INTRAGENIC DELETION OF THE GLI3 GENE
A MOUSE MODEL OF GREIG CEPHALOPOLYSYNDACTYLY SYNDROME - THE EXTRA-TOES(J) MUTATION CONTAINS AN INTRAGENIC DELETION OF THE GLI3 GENE
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DOI：
10.1038/ng0393-241
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发表时间：
1993-03-01
期刊：
影响因子：
30.8
通讯作者：
JOYNER, AL
中科院分区：
文献类型：
--
作者：
HUI, CC;JOYNER, AL
格雷格头多并指综合征（GCPS）是一种影响肢体和颅面发育的常染色体显性遗传疾病。最近，已经提出人GL13基因是GCPS的候选基因。在这里，我们描述了额外的脚趾（Xt），这是一个小鼠模型的GCPS的分子特征。Xt杂合子显示颅面缺陷和多指（趾）表型与GCPS相似。我们表明，Gli3基因在Xt（J）突变体中表达的缺陷是由于该基因3'端的缺失。此外，发现小鼠突变体和人类综合征中受影响的结构与小鼠中Gli3的表达结构域相关。这些结果有力地表明，GL13功能的缺陷导致GCPS。
Greig cephalopolysyndactyly syndrome (GCPS) is an autosomal dominant disorder affecting limb and craniofacial development. Recently, the human GLl3 gene has been proposed to be a candidate gene for GCPS. Here we describe the molecular characterization of extra-toes (Xt), which is a mouse model of GCPS. The Xt heterozygotes show craniofacial defects and a polydactyly phenotype similar to GCPS. We show that a deficiency of Gli3 expression in the Xt(J) mutant is due to a deletion within the 3' end of the gene. Furthermore, structures affected in the mouse mutant and human syndrome were found to correlate with expression domains of Gli3 in mouse. These results strongly suggest that the deficiency of GLl3 function leads to GCPS.