A model of mucopolysaccharidosis type IIIB in pigs

Abstract

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.

Muscle Transcriptome Analysis Reveals Potential Candidate Genes and Pathways Affecting Intramuscular Fat Content in Pigs

“…Module GS (MS) was the mean value of GS of the module genes. According to the selection criteria for critical modules reported in previous studies, modules with MTRs > 0.30 and MS > 0.25 were considered as candidate modules for the following functional enrichment analysis ( Howard et al, 2017 ; Yang et al, 2018 ).…”

Molecular Bases of Neurodegeneration and Cognitive Decline, the Major Burden of Sanfilippo Disease

“…The MPS IIIA model also demonstrated mild cerebrocortical atrophy [56]. Cerebral and cerebellar atrophy, ventriculomegaly, and abnormalities in the intracerebral capsule, parietal lobes and the thalamus have been documented in the pig model of MPS IIIB at 180 and 240 days of life, however no major alterations in density of Purkinje cells were observed [61].…”

“…A specific model for studying the neuropathology of MPS IIIA was generated in Drosophila and showed a knockdown of SGSH limited to neurons [60]. In addition, a NAGLU heterozygous model was recently developed in large white boars and presented with common symptoms found in MPS IIIB patients, such as slow growth, early death, somatic changes and cerebral abnormalities [61]. Mouse models also show a clinical phenotype close to that seen in patients and have been used extensively in the study of MPS III.…”

IRLnc: A novel functional noncoding RNA contributes to intramuscular fat deposition

“…One gene named LRRC66 was involved in diverse biological processes, including cell adhesion, cellular tra cking, and hormone-receptor interactions [28]. And other genes were mainly associated with diseases such as Mucopolysaccharidosis IIIB [29], stress-induced injury [30], oral-facial-digital syndromes [31], and breast cancer [32]. From the results, intramuscular related genes involved in fat and muscle related function were consistent with previous research, which reported that IMF is regulated through a complex pathway that interacts with muscle, fat, and connective tissue [33,34].…”