TY - JOUR
AU1 - Sancho-Pelluz, Javier
AU2 - Cui, Xuan
AU3 - Lee, Winston
AU4 - Tsai, Yi-Ting
AU5 - Wu, Wen-Hsuan
AU6 - Justus, Sally
AU7 - Washington, Ilyas
AU8 - Hsu, Chun-Wei
AU9 - Park, Karen
AU1 - Koch, Susanne
AU1 - Velez, Gabriel
AU1 - Bassuk, Alexander
AU1 - Mahajan, Vinit
AU1 - Lin, Chyuan-Sheng
AU1 - Tsang, Stephen
AB - 
D190N, a missense mutation in rhodopsin, causes photoreceptor degeneration in patients with autosomal dominant retinitis pigmentosa (adRP). Two competing hypotheses have been developed to explain why D190N rod photoreceptors degenerate: (a) defective rhodopsin trafficking prevents proteins from correctly exiting the endoplasmic reticulum, leading to their accumulation, with deleterious effects or (b) elevated mutant rhodopsin expression and unabated signaling causes excitotoxicity. A knock-in D190N mouse model was engineered to delineate the mechanism of pathogenesis. Wild type (wt) and mutant rhodopsin appeared correctly localized in rod outer segments of D190N heterozygotes. Moreover, the rhodopsin glycosylation state in the mutants appeared similar to that in wt mice. Thus, it seems plausible that the injurious effect of the heterozygous mutation is not related to mistrafficking of the protein, but rather from constitutive rhodopsin activity and a greater propensity for chromophore isomerization even in the absence of light.
TI - Mechanisms of neurodegeneration in a preclinical autosomal dominant retinitis pigmentosa knock-in model with a RhoD190N mutation
JF - Cellular and Molecular Life Sciences
DO - 10.1007/s00018-019-03090-9
DA - 2019-04-11
UR - https://www.deepdyve.com/lp/springer-journals/mechanisms-of-neurodegeneration-in-a-preclinical-autosomal-dominant-JerUy9PStm
SP - 3657
EP - 3665
VL - 76
IS - 18
DP - DeepDyve
ER -