ArticleHuman molecular genetics2003
Production of MPS VII mouse (Gus(tm(hE540A x mE536A)Sly)) doubly tolerant to human and mouse beta-glucuronidase.
Article in Human molecular genetics, 2003. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 21 citations in OpenAlex.
- Long-Term Liver-Targeted AAV8 Gene Therapy for Mucopolysaccharidosis IVA.Current issues in molecular biology · 2025Article
- Evaluation of AAV vectors with tissue-specific or ubiquitous promoters in a mouse model of mucopolysaccharidosis type IVA.Molecular therapy. Methods & clinical development · 2025Article
- Polymer-based drug delivery systems under investigation for enzyme replacement and other therapies of lysosomal storage disorders.Advanced drug delivery reviews · 2023Review
- Sex Difference Leads to Differential Gene Expression Patterns and Therapeutic Efficacy in Mucopolysaccharidosis IVA Murine Model Receiving AAV8 Gene Therapy.International journal of molecular sciences · 2022Article
- Liver-Targeted AAV8 Gene Therapy Ameliorates Skeletal and Cardiovascular Pathology in a Mucopolysaccharidosis IVA Murine Model.Molecular therapy. Methods & clinical development · 2020Article
- Growth Plate Pathology in the Mucopolysaccharidosis Type VI Rat Model-An Experimental and Computational Approach.Diagnostics (Basel, Switzerland) · 2020Article
- Beta-Glucuronidase Catalyzes Deconjugation and Activation of Curcumin-Glucuronide in Bone.Journal of natural products · 2019Article
- Chronic enzyme replacement therapy ameliorates neuropathology in alpha-mannosidosis mice.Annals of clinical and translational neurology · 2015Article
- Corrective GUSB transfer to the canine mucopolysaccharidosis VII cornea using a helper-dependent canine adenovirus vector.Journal of controlled release : official journal of the Controlled Release Society · 2014Article
- Corrective GUSB transfer to the canine mucopolysaccharidosis VII brain.Molecular therapy : the journal of the American Society of Gene Therapy · 2014Article
- Enzyme replacement therapy on hypophosphatasia mouse model.Journal of inherited metabolic disease · 2014Article
- A novel GUSB mutation in Brazilian terriers with severe skeletal abnormalities defines the disease as mucopolysaccharidosis VII.PloS one · 2012Article
- Enhancement of drug delivery: enzyme-replacement therapy for murine Morquio A syndrome.Molecular therapy : the journal of the American Society of Gene Therapy · 2010Article
- Mutations and polymorphisms in GUSB gene in mucopolysaccharidosis VII (Sly Syndrome).Human mutation · 2009Review
- Contribution of the H63D mutation in HFE to murine hereditary hemochromatosis.Proceedings of the National Academy of Sciences of the United States of America · 2003Article
- Induction of tolerance to human arylsulfatase A in a mouse model of metachromatic leukodystrophy.Molecular medicine (Cambridge, Mass.)Article
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Authors and funding
12 authors at 1 institution in 2 countries.
Funding
Abstract
Mucopolysaccharidosis VII (MPS VII, Sly syndrome) is an autosomal recessive lysosomal storage disease caused by beta-glucuronidase (GUS) deficiency. A naturally occurring mouse model of that disease has been very useful for studying experimental approaches to therapy. However, immune responses can complicate evaluation of the long-term benefits of enzyme replacement or gene therapy delivered to adult MPS VII mice. To make this model useful for studying the long-term effectiveness and side effects of experimental therapies delivered to adult mice, we developed a new MPS VII mouse model, which is tolerant to both human and murine GUS. To achieve this, we used homologous recombination to introduce simultaneously a human cDNA transgene expressing inactive human GUS into intron 9 of the murine Gus gene and a targeted active site mutation (E536A) into the adjacent exon 10. When the heterozygote products of germline transmission were bred to homozygosity, the homozygous mice expressed no GUS enzyme activity but expressed inactive human GUS protein highly and were tolerant to immune challenge with human enzyme. Expression of the mutant murine Gus gene was reduced to about 10% of normal levels, but the inactive murine GUS enzyme also conferred tolerance to murine GUS. This MPS VII mouse model should be useful to evaluate therapeutic responses in adult mice receiving repetitive doses of enzyme or mice receiving gene therapy as adults. Heterozygotes expressed only 9.5-26% of wild-type levels of murine GUS instead of the expected 50%, indicating a dominant-negative effect of the mutant enzyme monomers on the activity of GUS tetramers in different tissues. Corrective gene therapy in this model should provide high enough levels of expression of normal GUS monomers to overcome the dominant negative effect of mutant monomers on newly synthesized GUS tetramers in most tissues.
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