Heterozygous Loss of Yap1 in Mice Causes Progressive Cataracts.
Heterozygous Loss of Yap1 in Mice Causes Progressive Cataracts.
复制标题
DOI：
10.1167/iovs.61.12.21
复制
发表时间：
2020-10-01
影响因子：
4.4
通讯作者：
Li Q
中科院分区：
文献类型：
--
作者：
Lu Q;Zhang Y;Kasetti RB;Gaddipati S;Cvm NK;Borchman D;Li Q
Yap1 编码一种进化上保守的转录共激活因子，并作为 Hippo 信号通路的下游效应器发挥作用，控制组织大小和细胞生长。 Yap1 有助于晶状体上皮的发育。然而，Yap1单倍体缺陷对晶状体上皮的影响及其在白内障发生中的作用尚未见报道。本研究的目的是研究Yap1在晶状体上皮细胞（LEC）中的功能及其调控机制。通过目视观察和组织学和生化方法研究了 Yap1 杂合突变小鼠的晶状体表型。原代LEC培养物用于研究调节分子机制。小鼠中 Yap1 的杂合失活导致成年期白内障，且 LEC 表型有缺陷。尽管包括晶状体在内的眼睛早期发育正常，但大多数 Yap1 杂合子在出生后的前 6 个月内出现了白内障。白内障发生之前，晶状体上皮存在多种形态缺陷，包括细胞密度降低和细胞连接异常。 LEC 密度低与 LEC 增殖减少同时发生。此外，Yap1+/- LEC中Yap1靶基因Crim1的表达降低，而Crim1的过度表达可恢复Yap1+/- LEC细胞的体外增殖。 Yap1 基因的纯合性对于维持 LEC 持续增殖和维持正常大小的晶状体所需的 Crim1 充分表达至关重要。 Yap1 单倍体缺陷会导致白内障。
Yap1 encodes an evolutionarily conserved transcriptional coactivator and functions as a down-stream effector of the Hippo signaling pathway that controls tissue size and cell growth. Yap1 contributes to lens epithelial development. However, the effect of Yap1 haplodeficiency on the lens epithelium and its role in the development of cataracts has not been reported. The aim of the current study is to investigate Yap1 function and its regulatory mechanisms in lens epithelial cells (LECs). Lens phenotypes were investigated in Yap1 heterozygous mutant mice by visual observation and histological and biochemical methods. Primary LEC cultures were used to study regulatory molecular mechanism. The heterozygous inactivation of Yap1 in mice caused cataracts during adulthood with defective LEC phenotypes. Despite a normal early development of the eye including the lens, the majority of Yap1 heterozygotes developed cataracts in the first six months of age. Cataract was preceded by multiple morphological defects in the lens epithelium, including decreased cell density and abnormal cell junctions. The low LEC density was coincident with reduced LEC proliferation. In addition, expression of the Yap1 target gene Crim1 was reduced in the Yap1+/− LEC, and overexpression of Crim1 restored Yap1+/− LEC cell proliferation in vitro. Homozygosity of the Yap1 gene was critical for adequate Crim1 expression needed to maintain the constant proliferation of LEC and to maintain a normal-sized lens. Yap1 haplodeficiency leads to cataracts.
登录
查看更多内容
影响因子：
4.4
作者：
Hamon A;Masson C;Bitard J;Gieser L;Roger JE;Perron M
通讯作者：
Perron M
影响因子：
3.5
作者：
Beleggia, Filippo;Li, Yun;Wollnik, Bernd
通讯作者：
Wollnik, Bernd
影响因子：
16.6
作者：
Lee, Joanna Y.;Chang, Jessica K.;Chaudhuri, Ovijit
通讯作者：
Chaudhuri, Ovijit
影响因子：
64.5
作者：
Dong, Jixin;Feldmann, Georg;Pan, Duojia
通讯作者：
Pan, Duojia
影响因子：
7.7
作者：
Neto, Filipa;Klaus-Bergmann, Alexandra;Gerhardt, Holger
通讯作者：
Gerhardt, Holger