A model of mucopolysaccharidosis type IIIB in pigs
Qiang Yang,
Xueyan Zhao,
Yuyun Xing,
Chao Jiang,
Kai Jiang,
Pan Xu,
Weiwei Liu,
Jun Ren,
Lusheng Huang
Affiliations
Qiang Yang
State Key Laboratory of Pig Genetic Improvement and Production Technology, College of Animal Science and Technology, Jiangxi Agricultural University, Nanchang 330045, China
Xueyan Zhao
State Key Laboratory of Pig Genetic Improvement and Production Technology, College of Animal Science and Technology, Jiangxi Agricultural University, Nanchang 330045, China
Yuyun Xing
State Key Laboratory of Pig Genetic Improvement and Production Technology, College of Animal Science and Technology, Jiangxi Agricultural University, Nanchang 330045, China
Chao Jiang
State Key Laboratory of Pig Genetic Improvement and Production Technology, College of Animal Science and Technology, Jiangxi Agricultural University, Nanchang 330045, China
Kai Jiang
State Key Laboratory of Pig Genetic Improvement and Production Technology, College of Animal Science and Technology, Jiangxi Agricultural University, Nanchang 330045, China
Pan Xu
State Key Laboratory of Pig Genetic Improvement and Production Technology, College of Animal Science and Technology, Jiangxi Agricultural University, Nanchang 330045, China
Weiwei Liu
State Key Laboratory of Pig Genetic Improvement and Production Technology, College of Animal Science and Technology, Jiangxi Agricultural University, Nanchang 330045, China
Jun Ren
State Key Laboratory of Pig Genetic Improvement and Production Technology, College of Animal Science and Technology, Jiangxi Agricultural University, Nanchang 330045, China
Lusheng Huang
State Key Laboratory of Pig Genetic Improvement and Production Technology, College of Animal Science and Technology, Jiangxi Agricultural University, Nanchang 330045, China
Mucopolysaccharidosis type IIIB (MPS IIIB) is a rare genetic disorder caused by loss-of-function mutations in the NAGLU 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 NAGLU-deficient (NAGLU+/-) Large White boar via a transgenic approach. Here we characterized phenotypes of the F1 offspring of this founder to establish a pig model for MPS IIIB. qRT-PCR revealed that the NAGLU expression level was significantly decreased in a variety of tissues in NAGLU+/− pigs. ELISA assays showed obvious deficiency of NAGLU and higher (P<0.05) glycosaminoglycan levels in multiple tissues from NAGLU+/− pigs. NAGLU+/− pigs grew at a significantly (P<0.05) slower rate than control animals (NAGLU+/+). Death, mostly sudden death, occurred at all ages in NAGLU+/− pigs, most of which died within two years. Necropsy findings included pleural adhesions, lung shrinkage and abnormalities in the pericardium and mild hepatomegaly in NAGLU+/− pigs. Notable pathological changes were observed in the sections of brain, liver, spleen and kidney from NAGLU+/− pigs. Brain atrophy, ventriculomegaly, cerebellar atrophy and abnormalities in the intracerebral capsule, parietal lobes and the thalamus were also evident in NAGLU+/− 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.
