Affiliation:
1. Telethon Institute of Genetics and Medicine, TIGEM Pozzuoli (Naples) Italy
2. Department of Molecular Medicine and Medical Biotechnology University of Naples Federico II Naples Italy
3. Department of Clinical Medicine and Surgery University of Naples Federico II Naples Italy
4. Department of Biology University of Naples Federico II Naples Italy
Abstract
AbstractThe skeletal dysplasia spondyloepiphyseal dysplasia tarda (SEDT) is caused by mutations in the TRAPPC2 gene, 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 orthologous TRAPPC2 gene (olSedl) of Oryzias latipes (medaka) fish. OlSedl deficiency 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 function in vivo, we provide evidence for a mechanistic link between TRAPPC2‐mediated membrane trafficking, Col2 export, and developmental disorders.
Funder
Fondazione Telethon
Associazione Italiana per la Ricerca sul Cancro
Università degli Studi di Napoli Federico II
Subject
Cell Biology,Genetics,Molecular Biology,Biochemistry,Structural Biology