huPRPF31(2) Mouse

The PRPF31 gene, located on chromosome 19q13.4, encodes the PRP31 protein, a crucial component of the spliceosome, a large molecular machine essential for pre-mRNA splicing. This gene is ubiquitously expressed, meaning it is active in nearly all cell types and tissues throughout the body, as its function is fundamental to general cell metabolism and survival ^[1]. The encoded protein, also known as Protein 61K, plays a critical role in the assembly of the U4/U6·U5 tri-snRNP complex, a vital step in the splicing process ^[2]. Mutations in the PRPF31 gene are primarily associated with autosomal dominant retinitis pigmentosa (adRP), a progressive inherited retinal disease. Although the gene is expressed ubiquitously, the disease phenotype is retina-specific, with cellular labeling and studies showing that photoreceptor and retinal pigment epithelial (RPE) cells are the most affected, leading to their dysfunction and death ^[3]. This is often attributed to haploinsufficiency, where a single mutated copy of the gene is not sufficient to produce the necessary amount of functional protein, particularly in the retina, which has a high demand for splicing activity ^[4].

The huPRPF31(2) mouse model was generated by replacing the sequences from 5'UTR to 3'UTR of the endogenous mouse Prpf31 gene with the sequences from 5'UTR to 3'UTR of the human PRPF31 gene. This model can be used to study the pathological mechanisms and therapeutic approaches for autosomal dominant retinitis pigmentosa (adRP), as well as for the development of PRPF31-targeted drugs.