Recent insights into the mechanisms underlying light-dependent retinal degeneration from X. laevis models of retinitis pigmentosa.
We have recently developed transgenic X. laevis models of retinitis pigmentosa based on the rhodopsin P23H mutation in the context of rhodopsin cDNAs derived from several different species. The mutant rhodopsin in these animals is expressed at low levels, with levels of export from the endoplasmic reticulum to the outer segment that depend on the cDNA context. Retinal degeneration in these models demonstrates varying degrees of light dependence, with the highest light dependence coinciding with the highest ER export efficiency. Rescue of light dependent retinal degeneration by dark rearing is in turn dependent on the capacity of the mutant rhodopsin to bind chromophore. Our results indicate that rhodopsin chromophore can act in vivo as a pharmacological chaperone for P23H rhodopsin, and that light-dependent retinal degeneration caused by P23H rhodopsin is due to reduced chromophore binding.
Department of Ophthalmology and Visual Sciences, UBC/VGH Eye Care Centre, Vancouver, Canada. olmoritz@interchange.ubc.ca
Orson L
OL
Moritz
Beatrice M
BM
Tam
D000818:Animals; D004195:Disease Models, Animal; D004721:Endoplasmic Reticulum / Q000378:metabolism / Q000473:pathology / Q000528:radiation effects; D008027:Light; D008954:Models, Biological; D050505:Mutant Proteins / Q000378:metabolism; D012162:Retinal Degeneration / Q000150:complications* / Q000473:pathology; D012174:Retinitis Pigmentosa / Q000150:complications* / Q000473:pathology; D012243:Rhodopsin / Q000235:genetics / Q000378:metabolism; D014982:Xenopus laevis
D050505:Mutant Proteins; D012243:Rhodopsin