Role of trafficking protein particle complex 2 in medaka development

Abstract

AbstractThe skeletal dysplasia spondyloepiphyseal dysplasia tarda (SEDT) is caused by mutations in theTRAPPC2gene, which encodes Sedlin, a component of the trafficking protein particle (TRAPP) complex that we have shown previously to be required for the export of type II collagen (Col2) from the endoplasmic reticulum. No vertebrate model for SEDT has been generated thus far. To address this gap, we generated a Sedlin knockout animal by mutating the orthologousTRAPPC2gene (olSedl) ofOryzias latipes(medaka) fish.OlSedldeficiency leads to embryonic defects, short size, diminished skeletal ossification, and altered Col2 production and secretion, resembling human defects observed in SEDT patients. Moreover, SEDT knock-out animals display photoreceptor degeneration and gut morphogenesis defects, suggesting a key role for Sedlin in the development of these organs. Thus, by studying Sedlin functionin vivo, we provide evidence for a mechanistic link between TRAPPC2-mediated membrane trafficking, Col2 export, and developmental disorders.