Mutations in the homeobox gene HESX1/Hesx1 associated with septo-optic dysplasia in human and mouse
Mutations in the homeobox gene HESX1/Hesx1 associated with septo-optic dysplasia in human and mouse
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DOI：
10.1038/477
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发表时间：
1998-06-01
期刊：
影响因子：
30.8
通讯作者：
Robinson, ICAF
中科院分区：
文献类型：
--
作者：
Dattani, MT;Martinez-Barbera, JP;Robinson, ICAF
在小鼠发育的早期，同源盒基因Hesx 1在预期的前脑组织中表达，但后来变得局限于Rathke囊，垂体前叶的原基。缺乏Hesx 1的小鼠表现出不同的前中枢神经系统缺陷和垂体发育不良。突变体前脑减少，无眼症或小眼症，嗅觉发育缺陷和Rathke囊分叉。新生儿的胼胝体、前连合、海马连合和透明隔出现异常。在人类中，一种可比较且同样可变的表型是视隔发育不良（SOD）。我们克隆了人类HESX 1，并在受影响的个体中筛选突变。两个兄弟姐妹与SOD纯合的Arg 53 Cys错义突变内HESX 1同源结构域破坏其结合靶DNA的能力。这些数据表明Hesx 1/HESX 1在小鼠和人的前脑、中线和垂体发育中起重要作用。
During early mouse development the homeobox gene Hesx1 is expressed in prospective forebrain tissue, but later becomes restricted to Rathke's pouch, the primordium of the anterior pituitary gland. Mice lacking Hesx1 exhibit variable anterior CNS defects and pituitary dysplasia. Mutants have a reduced prosencephalon, anopthalmia or micropthalmia, defective olfactory development and bifurcations in Rathke's pouch. Neonates exhibit abnormalities in the corpus callosum, the anterior and hippocampal commissures, and the septum pellucidum. A comparable and equally variable phenotype in humans is septo-optic dysplasia (SOD). We have cloned human HESX1 and screened for mutations in affected individuals. Two siblings with SOD were homozygous for an Arg53Cys missense mutation within the HESX1 homeodomain which destroyed its ability to bind target DNA. These data suggest an important role for Hesx1/HESX1 in forebrain, midline and pituitary development in mouse and human.