Analysis of Pax6 Contiguous Gene Deletions in the Mouse, Mus musculus, Identifies Regions Distinct from Pax6 Responsible for Extreme Small-Eye and Belly-Spotting Phenotypes
Analysis of Pax6 Contiguous Gene Deletions in the Mouse, Mus musculus, Identifies Regions Distinct from Pax6 Responsible for Extreme Small-Eye and Belly-Spotting Phenotypes
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DOI：
10.1534/genetics.109.104562
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发表时间：
2009-08-01
期刊：
影响因子：
3.3
通讯作者：
Zaus, Irmgard
中科院分区：
文献类型：
--
作者：
Favor, Jack;Bradley, Alan;Zaus, Irmgard
在小鼠中，pax6功能以剂量依赖性方式对适当的眼睛发育至关重要。pax6基因缺失显示在早期胚胎阶段是纯合致死的。杂合子表现为腹部斑点和极端小眼症。眼表型比杂合pax6、基因内无效突变体更严重，提高了缺失在功能上不同的可能性。来自基因内无效突变，或者缺失中包含的与Pax6不同的区域影响眼睛表型。我们恢复并鉴定了在三个新的Pax6缺失中缺失的确切区域。在胚胎早期阶段，所有这些都是纯合子致死的。没有一个人的腹部有斑点。一个表达极端小眼症，两个表达类似于Pax6基因内无效突变体的温和的眼睛表型。Pax6表达水平和主要亚型的分析排除了表达极端小眼症的缺失直接归因于pax6的作用并且在功能上不同于基因内无效突变的假设。与Pax6不同的含有八个基因的区域被鉴定为钟形），斑点。含有一个基因（Rcn I）的第二个区域被鉴定为极端小眼表型。Rcn1是一种Ca（+2）结合蛋白，存在于内质网中，参与分泌途径并在眼内表达。我们的研究结果表明，在Pax6连续基因缺失中，Rcn1的缺失直接或间接导致了眼表型。
In the mouse pax6 function is critical in a dose-dependent manner for proper eye development. pax6 Configuous gene deletions were shown to be homozygous lethal at an early embryonic stage. Heterozygotes express belly spotting and extreme microphthalmia. The eye phenotype is more Severe than in heterozygous pax6, intragenic null mutants, raising the possibility that deletions are functionally different. from intragenic null mutations or that a region distinct from Pax6 included in the deletions affects eye phenotype. we recovered and identified the exact regions deleted in three new Pax6 deletions. All are homozygous lethal at an early embryonic stage. None express belly spotting. One expresses extreme microphthalmia and two express the milder eye phenotype similar to Pax6 intragenic null mutants. Analysis of Pax6 expression levels and the major isoforms excluded the hypothesis that the deletions expressing extreme microphthalmia are directly due to the action of pax6 and functionally different from intragenic null mutations. A region distinct from Pax6 containing eight genes was identified for bell), spotting. A second region containing one gene (Rcn I) was identified for the extreme microphthalmia phenotype. Rcn1 is a Ca(+2) -binding protein, resident in the endoplasmic reticulum, participates in the secretory pathway and expressed in the eye. Our results suggest that deletion of Rcn1 directly or indirectly contributes to the eye phenotype in Pax6 contiguous gene deletions.