A novel missense mutation of Mip causes semi-dominant cataracts in the Nat mouse

作者：Takahashi Gou; Hasegawa Sayaka; Fukutomi Yukiko; Harada Chihiro; Furugori Masamune; Seki Yuta; Kikkawa Yoshiaki; Wada Kenta^*

来源：Experimental Animals, 2017, 66(3): 271-282.

DOI：10.1538/expanim.17-0012

• congenital cataract
• MIP
• missense mutation
• mouse
• semi-dominant cataract

Major intrinsic protein of lens fiber (MIP) is one of the proteins essential for maintaining lens transparency while also contributing to dominant cataracts in humans. The Nodai cataract (Nat) mice harbor a spontaneous mutation in Mip and develop early -onset nuclear cataracts. The Nat mutation is a c.631G>A mutation (Mip(Nat),) resulting in a glycine-to-arginine substitution (p.Gly211Arg) in the sixth transmembrane domain. The Mip(Nat/Nat)homozygotes exhibit congenital cataracts caused by the degeneration of lens fiber cells. MIP normally localizes to the lens fiber cell membranes. However, the Mip(Nat/Nat) mice were found to lack an organelle-free zone, and the MIP was mislocalized to the nuclear membrane and perinuclear region. Furthermore, the Mip(Nat/Nat) mice exhibited milder cataracts than Mip(Nat/Nat) mice due to the slight degeneration of the lens fiber cells. Although there were no differences in the localization of MIP to the membranes of lens fiber cells in Mip(Nat/Nat) mice compared to that in wild-type mice, the protein levels of MIP were significantly reduced in the eyes. These findings suggest that cataractogenesis in Mip(Nat) mutants are caused by defects in MIP expression. Overall, the Mip(Nat) mice offer a novel model to better understand the phenotypes and mechanisms for the development of cataracts in patients that carry missense mutations in MIP.

• 出版日期2017-7
• 单位河北医科大学