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Sci Rep 2020 Aug 13;101:13757. doi: 10.1038/s41598-020-70735-2.
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CRISPR/Cas9 mediated mutation of the mtnr1a melatonin receptor gene causes rod photoreceptor degeneration in developing Xenopus tropicalis.

Wiechmann AF , Martin TA , Horb ME .

Nighttime surges in melatonin levels activate melatonin receptors, which synchronize cellular activities with the natural light/dark cycle. Melatonin receptors are expressed in several cell types in the retina, including the photon-sensitive rods and cones. Previous studies suggest that long-term photoreceptor survival and retinal health is in part reliant on melatonin orchestration of circadian homeostatic activities. This scenario would accordingly envisage that disruption of melatonin receptor signaling is detrimental to photoreceptor health. Using in vivo CRISPR/Cas9 genomic editing, we discovered that a small deletion mutation of the Mel1a melatonin receptor (mtnr1a) gene causes a loss of rod photoreceptors in retinas of developing Xenopus tropicalis heterozygous, but not homozygous mutant tadpoles. Cones were relatively spared from degeneration, and the rod loss phenotype was not obvious after metamorphosis. Localization of Mel1a receptor protein appeared to be about the same in wild type and mutant retinas, suggesting that the mutant protein is expressed at some level in mutant retinal cells. The severe impact on early rod photoreceptor viability may signify a previously underestimated critical role in circadian influences on long-term retinal health and preservation of sight. These data offer evidence that disturbance of homeostatic, circadian signaling, conveyed through a mutated melatonin receptor, is incompatible with rod photoreceptor survival.

PubMed ID: 32792587
PMC ID: PMC7426423
Article link: Sci Rep
Grant support: [+]

Species referenced: Xenopus tropicalis
Genes referenced: mtnr1a mtnr1b pam psmd6 rpe
GO keywords: photoreceptor cell development
Antibodies: Mtnr1b Ab1
gRNAs referenced: mtnr1a gRNA1 mtnr1a gRNA2 mtnr1a gRNA3 mtnr1a gRNA4

Phenotypes: Xtr + mtnr1a sgRNAs (Fig 4 a b ) [+]

Article Images: [+] show captions
References [+] :
Anders, In vitro enzymology of Cas9. 2015, Pubmed