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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 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-deficie...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
The Company of Biologists Ltd
2018
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6215415/ https://www.ncbi.nlm.nih.gov/pubmed/30257828 http://dx.doi.org/10.1242/bio.035386 |
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author | Yang, Qiang Zhao, Xueyan Xing, Yuyun Jiang, Chao Jiang, Kai Xu, Pan Liu, Weiwei Ren, Jun Huang, Lusheng |
author_facet | Yang, Qiang Zhao, Xueyan Xing, Yuyun Jiang, Chao Jiang, Kai Xu, Pan Liu, Weiwei Ren, Jun Huang, Lusheng |
author_sort | Yang, Qiang |
collection | PubMed |
description | 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 (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. |
format | Online Article Text |
id | pubmed-6215415 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | The Company of Biologists Ltd |
record_format | MEDLINE/PubMed |
spelling | pubmed-62154152018-11-05 A model of mucopolysaccharidosis type IIIB in pigs Yang, Qiang Zhao, Xueyan Xing, Yuyun Jiang, Chao Jiang, Kai Xu, Pan Liu, Weiwei Ren, Jun Huang, Lusheng Biol Open Research Article 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 (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. The Company of Biologists Ltd 2018-09-26 /pmc/articles/PMC6215415/ /pubmed/30257828 http://dx.doi.org/10.1242/bio.035386 Text en © 2018. Published by The Company of Biologists Ltd http://creativecommons.org/licenses/by/3.0This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution and reproduction in any medium provided that the original work is properly attributed. |
spellingShingle | Research Article Yang, Qiang Zhao, Xueyan Xing, Yuyun Jiang, Chao Jiang, Kai Xu, Pan Liu, Weiwei Ren, Jun Huang, Lusheng A model of mucopolysaccharidosis type IIIB in pigs |
title | A model of mucopolysaccharidosis type IIIB in pigs |
title_full | A model of mucopolysaccharidosis type IIIB in pigs |
title_fullStr | A model of mucopolysaccharidosis type IIIB in pigs |
title_full_unstemmed | A model of mucopolysaccharidosis type IIIB in pigs |
title_short | A model of mucopolysaccharidosis type IIIB in pigs |
title_sort | model of mucopolysaccharidosis type iiib in pigs |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6215415/ https://www.ncbi.nlm.nih.gov/pubmed/30257828 http://dx.doi.org/10.1242/bio.035386 |
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