A model o mucopolysaccharidosis type IIIB in pigs

文献类型： 外文期刊

第一作者： Yang, Qiang

作者： Yang, Qiang;Zhao, Xueyan;Xing, Yuyun;Jiang, Chao;Jiang, Kai;Xu, Pan;Liu, Weiwei;Ren, Jun;Huang, Lusheng;Zhao, Xueyan

作者机构：

关键词： MPS IIIB; Lysosomal storage disease; NAGLU; Pig model

期刊名称：BIOLOGY OPEN （ 影响因子：2.422； 五年影响因子：2.647 ）

ISSN： 2046-6390

年卷期： 2018 年 7 卷 10 期

页码：

收录情况： SCI

摘要： 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 F-1 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 (NAGLUl. 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.

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