Foxe3 is required for morphogenesis and differentiation of the anterior segment of the eye and is sensitive to Pax6 gene dosage
Foxe3 is required for morphogenesis and differentiation of the anterior segment of the eye and is sensitive to Pax6 gene dosage
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DOI：
10.1016/j.ydbio.2006.09.021
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发表时间：
2007-02-01
影响因子：
2.7
通讯作者：
Carlsson, Peter
中科院分区：
文献类型：
--
作者：
Blixt, Asa;Landgren, Henrik;Carlsson, Peter
发育不良的透镜（dyl）小鼠突变体在Foxe 3中有突变，其通过编码的叉头转录因子抑制DNA结合。在这里，我们证实，通过靶向失活，Foxe 3突变是dyl表型，其中包括损失的透镜上皮细胞，一个小的，白内障透镜，和失败的透镜从表面外胚层脱离负责。与靶向Foxe 3的最近报道相反，当比较同源菌株时，我们发现dyl和Foxe 3（-/-）突变体之间没有表型差异，因此没有任何证据反对Foxe 3（dyl）是无效等位基因。除透镜外，前段的大多数组织虹膜、角膜、睫状体和小梁网畸形或显示分化缺陷。尽管这些小鼠具有完整的透镜上皮，但许多这些异常，如虹膜-角膜和虹膜-晶状体粘连，在Foxe 3突变杂合子小鼠中以不太严重的形式存在。早期Foxe 3表达对Pax 6基因剂量减半高度敏感，并且Pax 6和Foxe 3突变体之间存在显著的表型相似性。因此，我们认为许多与Pax 6单倍不足相关的眼部畸形是Foxe 3表达减少的结果。(c)2006年爱思唯尔公司All rights reserved.
The dysgenetic lens (dyl) mouse mutant has mutations in Foxe3, which inactivate DNA binding by the encoded forkhead transcription factor. Here we confirm, by targeted inactivation, that Foxe3 mutations are responsible for the dyl phenotype, which include loss of lens epithelium; a small, cataractic lens; and failure of the lens to detach from the surface ectoderm. In contrast to a recent report of targeted Foxe3, we found no phenotypic difference between dyl and Foxe3(-/-) mutants when congenic strains were compared, and thus nothing that argues against Foxe3(dyl) being a null allele. In addition to the lens, most tissues of the anterior segment-iris, cornea, ciliary body and trabecular meshwork-are malformed or show differentiation defects. Many of these abnormalities, such as irido-corneal and irido-lenticular adherences, are present in a less severe form in mice heterozygous for the Foxe3 mutation, in spite of these having an intact lens epithelium. Early Foxe3 expression is highly sensitive to a halved Pax6 gene dosage and there is a striking phenotypic similarity between Pax6 and Foxe3 mutants. We therefore propose that many of the ocular malformations associated with Pax6 haploinsufficiency are consequences of a reduced expression of Foxe3. (c) 2006 Elsevier Inc. All rights reserved.