Deficiency in the expression of Vps13C is associated with altered retinal and lens development in mice

Abstract

SummaryWhile performing genotyping screening in the German Mouse Clinic we identified the Vps13C mouse mutant with eye phenotype where the homozygous mutant mice show signs of neurodegeneration, indicated by a reduction in the total retinal thickness, additionally the retinal blood vessels showed a pattern with structural alteration. Eye histology revealed the display of lipid‐like droplets in the retinal layers and in the anterior lens matrix. VPS 13C is a member of the VPS13 family of vacuolar protein sorting‐associated proteins highly conserved throughout eukaryotic evolution. While mutations in VPS13A and VPS13B cause the genetic diseases chorea‐acanthocytosis (ChAc) and Cohen syndrome, respectively, VSP13C is reported to be associated with Parkinsons disease and late onset Alzheimer's disease (LOAD). Moreover VPS13C has recently been found to be involved in the protein degradation through the ubiquitin being closely associated with lipid droplets and lysosomes. Human diseases are caused by the dysregulated accumulation of ubiquitinated protein aggregates, including neurodegenerative disorders. We believe Vps13c could open novel avenues for uncovering new treatments of metabolic and neurodegenerative disorders.