Development of a novel humanized Knockin mouse of retinitis pigmentosa with IMPDH1 mutation

Abstract

Purpose: Retinitis pigmentosa causes blindness from retinal damage and has no cure. To advance treatment options, animal models with retinal degeneration are necessary. IMPDH1 is a gene associated with the disease, and an animal model with a mutated IMPDH1 gene has been developed for further research. Methods: Researchers used CRISPR-Cas9 to create a retinal degeneration model in mice with a human mutation. They replaced a nucleotide with ssODN and studied the mice's characteristics with imaging and tests until they were 7 months old. Results: At 4 weeks, genotypes show a difference in retina thickness. Wild types maintain the layer until 7 months; however, it thins after 4 weeks. Homozygotes experience retinal detachment around 8 weeks and severe degeneration by 7 months. Heterozygotes have thinner retinas and slower pigmentation progression. Conclusions: These results suggest that the phenotype appeared differently depending on the genotype (wild, heterozygote, and homozygote) of the produced IMPDH1 mutated humanized mouse. Accordingly, it was confirmed that the IMPDH1 gene is autosomal dominant, and the degree of symptoms varies depending on the genotype