Yang Qiang, Zhao Xueyan, Xing Yuyun, Jiang Chao, Jiang Kai, Xu Pan, Liu Weiwei, Ren Jun, Huang Lusheng
State Key Laboratory of Pig Genetic Improvement and Production Technology, College of Animal Science and Technology, Jiangxi Agricultural University, Nanchang 330045, China.
Shandong Provincial Key Laboratory of Animal Disease Control and Breeding, Institute of Animal Science and Veterinary Medicine, Shandong Academy of Agricultural Sciences, Jinan 250100, China.
Biol Open. 2018 Oct 26;7(10):bio035386. doi: 10.1242/bio.035386.
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.
ⅢB型黏多糖贮积症（MPS IIIB）是一种由该基因功能丧失性突变引起的罕见遗传疾病。猪是人类疾病理想的大型动物模型；然而，尚未有MPS IIIB猪模型的报道。我们之前通过转基因方法培育出了一只杂合子NAGLU缺陷（NAGLU -/-）的大白猪。在此，我们对这只奠基猪的F1代后代的表型进行了特征分析，以建立MPS IIIB的猪模型。qRT-PCR结果显示，NAGLU -/-猪多种组织中的NAGLU表达水平显著降低。ELISA分析表明，NAGLU -/-猪多个组织中NAGLU明显缺乏，糖胺聚糖水平更高（<0.05）。NAGLU -/-猪的生长速度明显（<0.05）慢于对照动物（野生型）。NAGLU -/-猪在各个年龄段均出现死亡，多数为猝死，其中大部分在两年内死亡。尸检结果包括NAGLU -/-猪的胸膜粘连、肺萎缩、心包异常以及轻度肝肿大。在NAGLU -/-猪的脑、肝、脾和肾切片中观察到显著的病理变化。NAGLU -/-猪还出现脑萎缩、脑室扩大、小脑萎缩以及脑内囊、顶叶和丘脑异常。总之，NAGLU -/-猪表现出人类MPS IIIB患者的典型症状，因此代表了一种新型的该疾病大型动物模型。本文配有对该论文第一作者的第一人称访谈。
