An L314Q mutation in Map3k1 gene results in failure of eyelid fusion in the N-ethyl-N-nitrosourea-induced mutant line

In this study, we describe an N-ethyl-N-nitrosourea-induced mouse model with a corneal opacity phenotype that was associated with eye open at birth (EOB). Histological and immunohistochemistry staining analysis showed abnormal differentiation of the corneal epithelial cells in the mutant mice. The EOB phenotype was dominantly inherited on a C57BL/6 (B6) background. This allele carries a T941A substitution in exon 4 that leads to an L314Q amino acid change in the open reading frame of MAP3K1 (MEEK1). We named this novel Map3k1 allele Map3k1(L314Q). Phalloidin staining of F-actin was reduced in the mutant epithelial leading edge cells, which is indicative of abnormality in epithelial cell migration. Interestingly enough, not only p-c-Jun and p-JNK but also c-Jun levels were decreased in the mutant epithelial leading edge cells. This study identifies a novel mouse Map3k1 allele causing EOB phenotype and the EOB phenotype in Map3k1(L314Q) mouse may be associated with the reduced level of p-JNK and c-Jun.

Automated summary

This study presents a novel mouse model with a corneal opacity phenotype associated with eye open at birth (EOB) caused by an N-ethyl-N-nitrosourea-induced mutation in the Map3k1 gene. The mutation led to abnormal differentiation of corneal epithelial cells and reduced levels of p-JNK and c-Jun in mutant cells. This research provides insights into the molecular mechanisms underlying the EOB phenotype in mice with the Map3k1(L314Q) allele.