Lyon M F, Bogani D, Boyd Y, Guillot P, Favor J
MRC Mammalian Genetics Unit, Harwell, Didcot, Oxfordshire, UK.
Mol Vis. 2000 Oct 31;6:199-203.
The work forms part of a major project to study the genetics of mouse cataract mutants found during the course of mutagenesis experiments. The long-term aim is to find the underlying gene mutation in each cataract mutant. Here we report further studies of the mutant cataract and curly whiskers (Ccw), previously mapped to Chromosome 4, and also investigations of the corneal opacity (Coop) mutant, which is shown to involve a mutation in the Pax6 gene.
For Ccw, the methods included mapping relative to microsatellite markers and histological studies. For the Coop mutant, breeding methods were used to show that Coop was allelic with Pax6. The Pax6 coding region in the mutant was then sequenced.
The Ccw locus was mapped to approximately position 45cM on the consensus map of Chr 4. Histologically, progressive degeneration of the lens was seen. In the Coop mutant, a base-pair change C->T was found at position 1033 in the Pax6 gene, which created a stop codon leading to premature termination of translation, and to a truncated Pax6 protein.
The phenotype in Ccw/+ heterozygotes involves a new type of lens degeneration in the mouse. On the basis of the phenotype and the locus position, no candidate gene has yet been identified. The Pax6coop mutant differs in phenotype from known null alleles of Pax6, implying that it is a hypomorph.
这项工作是一个重大项目的一部分，该项目旨在研究在诱变实验过程中发现的小鼠白内障突变体的遗传学。长期目标是在每个白内障突变体中找到潜在的基因突变。在此，我们报告对先前定位到4号染色体的突变体白内障和卷曲胡须（Ccw）的进一步研究，以及对角膜混浊（Coop）突变体的调查，该突变体被证明涉及Pax6基因的突变。
对于Ccw，方法包括相对于微卫星标记进行定位和组织学研究。对于Coop突变体，采用育种方法证明Coop与Pax6等位。然后对突变体中的Pax6编码区进行测序。
Ccw基因座在4号染色体的共识图谱上被定位到大约45cM的位置。组织学上，可见晶状体进行性退变。在Coop突变体中，在Pax基因的1033位发现碱基对变化C->T，这产生了一个终止密码子，导致翻译提前终止，并产生截短的Pax6蛋白。
Ccw/+杂合子中的表型涉及小鼠中一种新型的晶状体退变。基于表型和基因座位置，尚未鉴定出候选基因。Pax6coop突变体的表型与已知的Pax6无效等位基因不同，这意味着它是一个亚效等位基因。
