{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T17:50:05Z","timestamp":1790272205300,"version":"4.1.0"},"reference-count":30,"publisher":"The Company of Biologists","license":[{"start":{"date-parts":[[2021,5,18]],"date-time":"2021-05-18T00:00:00Z","timestamp":1621296000000},"content-version":"am","delay-in-days":1233,"URL":"http:\/\/creativecommons.org\/licenses\/by\/3.0"}],"funder":[{"name":"National Key Research Program of China","award":["2016ZX08006-003"],"award-info":[{"award-number":["2016ZX08006-003"]}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["31525023"],"award-info":[{"award-number":["31525023"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"abstract":"<jats:p>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+\/\u2212) 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+\/\u2212 pigs. ELISA assays showed obvious deficiency of NAGLU and higher (P&amp;lt;0.05) glycosaminoglycan levels in multiple tissues from NAGLU+\/\u2212 pigs. NAGLU+\/\u2212 pigs grew at a significantly (P&amp;lt;0.05) slower rate than control animals (NAGLU+\/+). Death, mostly sudden death, occurred at all ages in NAGLU+\/\u2212 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+\/\u2212 pigs. Notable pathological changes were observed in the sections of brain, liver, spleen and kidney from NAGLU+\/\u2212 pigs. Brain atrophy, ventriculomegaly, cerebellar atrophy and abnormalities in the intracerebral capsule, parietal lobes and the thalamus were also evident in NAGLU+\/\u2212 pigs. Together, NAGLU+\/\u2212 pigs show typical symptoms of human MPS IIIB patients and thus represent a novel large-animal model for the disease.<\/jats:p>","DOI":"10.1242\/bio.035386","type":"journal-article","created":{"date-parts":[[2018,9,26]],"date-time":"2018-09-26T14:47:35Z","timestamp":1537973255000},"source":"Crossref","is-referenced-by-count":10,"title":["A model of mucopolysaccharidosis type IIIB in pigs"],"prefix":"10.1242","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9890-263X","authenticated-orcid":false,"given":"Qiang","family":"Yang","sequence":"first","affiliation":[{"name":"State Key Laboratory of Pig Genetic Improvement and Production Technology, Jiangxi Agricultural University, Nanchang, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8683-2569","authenticated-orcid":false,"given":"Xueyan","family":"Zhao","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Pig Genetic Improvement and Production Technology, Jiangxi Agricultural University, Nanchang, China"},{"name":"Shandong Provincial Key Laboratory of Animal Disease Control and Breeding, Institute of Animal Science and Veterinary Medicine, Shandong Academy of Agricultural Sciences, Jinan, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6433-3221","authenticated-orcid":false,"given":"Yuyun","family":"Xing","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Pig Genetic Improvement and Production Technology, Jiangxi Agricultural University, Nanchang, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4732-0787","authenticated-orcid":false,"given":"Chao","family":"Jiang","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Pig Genetic Improvement and Production Technology, Jiangxi Agricultural University, Nanchang, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9656-5767","authenticated-orcid":false,"given":"Kai","family":"Jiang","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Pig Genetic Improvement and Production Technology, Jiangxi Agricultural University, Nanchang, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9099-5651","authenticated-orcid":false,"given":"Pan","family":"Xu","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Pig Genetic Improvement and Production Technology, Jiangxi Agricultural University, Nanchang, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1302-0209","authenticated-orcid":false,"given":"Weiwei","family":"Liu","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Pig Genetic Improvement and Production Technology, Jiangxi Agricultural University, Nanchang, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6664-3998","authenticated-orcid":false,"given":"Jun","family":"Ren","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Pig Genetic Improvement and Production Technology, Jiangxi Agricultural University, Nanchang, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lusheng","family":"Huang","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Pig Genetic Improvement and Production Technology, Jiangxi Agricultural University, Nanchang, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"237","published-online":{"date-parts":[[2018,1,1]]},"reference":[{"key":"2021042423244886300_BIO035386C1","doi-asserted-by":"publisher","first-page":"254","DOI":"10.1016\/S0887-8994(01)00305-8","article-title":"Extraneurologic symptoms as presenting signs of Sanfilippo disease","volume":"25","author":"Barone","year":"2001","journal-title":"Pediatr. 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Drug Discov."},{"key":"2021042423244886300_BIO035386C10","doi-asserted-by":"publisher","first-page":"913","DOI":"10.1038\/gt.2013.14","article-title":"Disease correction by combined neonatal intracranial AAV and systemic lentiviral gene therapy in Sanfilippo Syndrome type B mice","volume":"20","author":"Heldermon","year":"2013","journal-title":"Gene Ther."},{"key":"2021042423244886300_BIO035386C11","doi-asserted-by":"publisher","first-page":"16406","DOI":"10.1038\/s41598-017-16618-5","article-title":"Deleting the mouse Hsd17b1 gene results in a hypomorphic Naglu allele and a phenotypemimicking a lysosomal storage disease","volume":"7","author":"Jokela","year":"2017","journal-title":"Sci. Rep."},{"key":"2021042423244886300_BIO035386C12","doi-asserted-by":"publisher","first-page":"358","DOI":"10.1007\/s10545-007-0539-5","article-title":"Bovine mucopolysaccharidosis type IIIB","volume":"30","author":"Karageorgos","year":"2007","journal-title":"J. Inherit. Metab. 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