A model of mucopolysaccharidosis type IIIB in pigs.

Mucopolysaccharidosis type IIIB (MPS IIIB) is a rare genetic disorder caused by loss-of-function mutations in the gene. 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 heterozygous -deficient ( ) Large White boar via a transgenic approach. Here we characterized phenotypes of the F offspring of this founder to establish a pig model for MPS IIIB. qRT-PCR revealed that the expression level was significantly decreased in a variety of tissues in pigs. ELISA assays showed obvious deficiency of NAGLU and higher (<0.05) glycosaminoglycan levels in multiple tissues from pigs. pigs grew at a significantly (<0.05) slower rate than control animals ( ). Death, mostly sudden death, occurred at all ages in pigs, most of which died within two years. Necropsy findings included pleural adhesions, lung shrinkage and abnormalities in the pericardium and mild hepatomegaly in pigs. Notable pathological changes were observed in the sections of brain, liver, spleen and kidney from pigs. Brain atrophy, ventriculomegaly, cerebellar atrophy and abnormalities in the intracerebral capsule, parietal lobes and the thalamus were also evident in pigs. Together, 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.