Retinal pigment epithelium degeneration caused by aggregation of PRPF31 and the role of HSP70 family of proteins

• DOI: 10.1186/s10020-019-0124-z
• Publication Date: 2019-12-31T13:02:43Z
• Authors: Lourdes Valdés-Sá...; Sofia M. Calado; Berta de la Cerda; Ana Aramburu; Ana Belén García-...; Simone Massalini; Adoración Montero...; Vaibhav Bhatia; Eduardo Rodríguez...; Andrea Diez-Lloret; Daniel Rodríguez-...; Christina Chakarova; Shom S. Bhattacharya; Francisco J. Díaz...
• Keywords: Haploinsufficiency; Mutant protein

Mutations in pre-mRNA splicing factor PRPF31 can lead to retinitis pigmentosa (RP). Although the exact disease mechanism remains unknown, it has been hypothesized that haploinsufficiency might be involved pathophysiology of disease.In this study, we have analyzed a mouse model containing p.A216P mutation Prpf31 gene.We found mutant protein produces cytoplasmic aggregates retinal pigment epithelium and decreasing levels nucleus. Additionally, normal was recruited insoluble when overexpressed vitro. In response aggregation, Hspa4l is overexpressed. This member HSP70 family chaperones contribute correct folding solubilization protein, allowing its translocation nucleus.Our data suggests dominant-negative degeneration due mutations PRPF31. over-expression new therapeutic target for treatment mutations.