Reduced PLP2 expression increases ER-stress-induced neuronal apoptosis and risk for adverse neurological outcomes after hypoxia ischemia injury.

ABSTRACT: Both genetic and environmental factors contribute to the development of intellectual disability (ID). Previously, we identified a promoter variant (-113C>A) in PLP2 (proteolipid protein 2) that results in an ∼4-fold reduction of transcript and protein and is overly represented in males with X-linked ID (XLID). The functional connection between reduced PLP2 expression and increased risk to XLID is unknown. To investigate the pathophysiological mechanisms, we studied a Plp2-loss-of-function murine model and fibroblasts from XLID patients hemizygous for PLP2-(-113C>A). We found that Plp2-deficient mouse embryonic fibroblast and human fibroblasts carrying PLP2-(-113C>A) have similarly defective endoplasmic reticulum (ER) trafficking, increased basal ER stress and exaggerated susceptibility to

SUBMITTER: Zhang L 

PROVIDER: S-EPMC4664164 | biostudies-literature | 2015 Dec

REPOSITORIES: biostudies-literature