Regulation of lens fiber cell differentiation by transcription factor c-Maf
Regulation of lens fiber cell differentiation by transcription factor c-Maf
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DOI：
10.1074/jbc.274.27.19254
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发表时间：
1999-07-02
影响因子：
4.8
通讯作者：
Yamamoto, M
中科院分区：
文献类型：
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作者：
Kawauchi, S;Takahashi, S;Yamamoto, M
为了阐明晶状体发育的调控机制，我们寻找了在小鼠晶状体中表达的Maf家族的成员，并发现了三个成员，c-Maf， MafB和Nrl。其中，晶状体中最早表达的因子是c-Maf。c-Maf在晶状体纤维细胞中表达最为突出，并在晶状体发育过程中持续表达。为了研究c-Maf对晶状体发育的功能贡献，我们分离了包含小鼠c-Maf基因的基因组克隆，并对其进行了靶向破坏。将β -半乳糖苷酶（lacZ）基因插入到c-maf位点，通过对lacZ活性的染色，可以看到c-maf在杂合突变小鼠中的积累情况。纯合子突变胚胎和新生儿缺乏正常的晶状体。组织学检查显示晶状体纤维细胞分化缺陷。晶体蛋白基因的表达在c-maf-null突变小鼠晶状体中严重受损。这些结果表明，c-Maf是小鼠发育过程中晶状体分化不可缺少的调节因子。
To elucidate the regulatory mechanisms underlying lens development, we searched for members of the large Maf family, which are expressed in the mouse lens, and found three, c-Maf, MafB, and Nrl. Of these, the earliest factor expressed in the lens was c-Maf. The expression of c-Maf was most prominent in lens fiber cells and persisted throughout lens development. To examine the functional contribution of c-Maf to lens development, we isolated genomic clones encompassing the murine c-maf gene and carried out its targeted disruption. Insertion of the beta-galactosidase (lacZ) gene into the c-maf locus allowed visualization of c-Maf accumulation in heterozygous mutant mice by staining for LacZ activity. Homozygous mutant embryos and newborns lacked normal lenses. Histological examination of these mice revealed defective differentiation of lens fiber cells. The expression of crystallin genes was severely impaired in the c-maf-null mutant mouse lens. These results demonstrate that c-Maf is an indispensable regulator of lens differentiation during murine development.