A model of mucopolysaccharidosis type IIIB in pigs

摘要

Mucopolysaccharidosis type IIIB (MPS IIIB) is a rare genetic disorder caused by loss-of-function mutations in theNAGLUgene. Pigs are an ideal large animal model for human diseases; however, a porcine model of MPS IIIB has not been reported. We have previously generated a heterozygousNAGLU-deficient (NAGLU+/-) Large White boar via a transgenic approach. Here we characterized phenotypes of the F1offspring of this founder to establish a pig model for MPS IIIB. qRT-PCR revealed that theNAGLUexpression level was significantly decreased in a variety of tissues inNAGLU+/?pigs. ELISA assays showed obvious deficiency of NAGLU and higher (P0.05) glycosaminoglycan levels in multiple tissues fromNAGLU+/?pigs.NAGLU+/?pigs grew at a significantly (P0.05) slower rate than control animals (NAGLU+/+). Death, mostly sudden death, occurred at all ages inNAGLU+/?pigs, most of which died within two years. Necropsy findings included pleural adhesions, lung shrinkage and abnormalities in the pericardium and mild hepatomegaly inNAGLU+/?pigs. Notable pathological changes were observed in the sections of brain, liver, spleen and kidney fromNAGLU+/?pigs. Brain atrophy, ventriculomegaly, cerebellar atrophy and abnormalities in the intracerebral capsule, parietal lobes and the thalamus were also evident inNAGLU+/?pigs. Together,NAGLU+/?pigs show typical symptoms of human MPS IIIB patients and thus represent a novel large animal model for the disease.This article has an associated First Person interview with the first author of the paper.