15-P038 Stra6.2: A novel member of the STRA6 gene family

Retinoids are vital for normal embryonic development and are necessary during postnatal development and adulthood for the maintenance of the reproductive and nervous system and for visual pigment synthesis. STRA6 (Stimulated by retinoic acid 6) is the cell surface receptor for retinol binding protein (RBP4), which facilitates the cellular uptake of retinol. Mutations in Stra6 are responsible for some cases of a birth defect syndrome known as PDAC (Pulmonary hypoplasia, Diaphragmatic hernia, Anopthalmia, Cardiac defects). The developmental disruption in this syndrome occurs in those systems that are affected in animal models of vitamin A deficiency (VAD) indicating the importance of STRA6 in providing cellular retinol during development. A bioinformatics approach identified a paralogue of STRA6, which has 18% identity at the protein level in mouse (STRA6.2) and also conserves many of the residues mutated in PDAC cases. Stra6.2 was found to have orthologues in diverse species, including Trichoplax adhaerens. Stra6.2 is well conserved amongst mammals, however, the gene has been split across the chromosome in great apes resulting in a functional C-terminus and a pseudogenised N-terminus with an associated break in synteny. Expression analysis in humans, however, confirms that mRNA from this truncated gene is expressed in tissues from the adult, foetus and in cell lines. In zebrafish, expression analysis indicates that both Stra6 and Stra6.2 transcripts are present and deposited maternally into the egg. Morpholino knockdown of the Stra6.2 transcript in zebrafish embryos is underway to determine if it has a similar role in development to that of STRA6.