Abstract:Pseudoxanthoma elasticum (PXE) is an autosomal recessive multi-system disease, manifesting pathologic mineralization of connective tissues, including the skin, eyes and cardiovascular system. The prevalence of PXE in population is about 1/50000. PXE is mainly caused by mutations in abcc6/mrp6, which encodes a member of the sub-family C of ATP-binding cassette (ABC) transport proteins. However, the roles of abcc6 for organogenesis and mechanisms remain largely unknown. We have constructed abcc6a mutant with the same conserved domain substitution of PXE disease (G1302R) using CRISPR/Cas9-mediated knock-in system in zebrafish. We observed similar symptoms of human PXE disease in abcc6a mutants. The establishment of PXE disease model in zebrafish provides insights into pathological mechanisms of PXE disease and opens novel avenues for developing potential therapy.
Keywords: PXE, ABCC6, disease model, zebrafish.