A single-base-pair deletion in the beta-glucuronidase gene accounts for the phenotype of murine mucopolysaccharidosis type VII.

Sands, Mark S.; Birkenmeier, Edward H.

doi:10.1073/pnas.90.14.6567

Cited by 119 publications

(54 citation statements)

References 21 publications

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“…A murine model of MPS VII has been described that has no detectable GUSB activity and is caused by a single base pair deletion in exon 10 of the murine gene. 3,5 The MPS VII mouse model recapitulates many of the symptoms seen in human patients, and has been widely used in the evaluation of therapeutic strategies for lysosomal storage diseases.…”

Section: Introductionmentioning

confidence: 99%

Prevention of systemic clinical disease in MPS VII mice following AAV-mediated neonatal gene transfer

et al. 2001

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Section: Introductionmentioning

confidence: 99%

Prevention of systemic clinical disease in MPS VII mice following AAV-mediated neonatal gene transfer

et al. 2001

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“…In mice, the mutation is a spontaneous, single base pair deletion that results in a frameshift and a subsequent stop codon in the sequence coding for the GUS protein. 5 Without GUS activity GAGs cannot be completely catabolized and therefore accumulate in the lysosomes to form stor-age granules or vacuoles in almost all tissues. This in turn results in animals that have distorted facial features, defects in skeletal development, dwarfism, reduced learning capacity, and early death at approximately 5 months of age.…”

Section: Introductionmentioning

confidence: 99%

Treatment of lysosomal storage disease in MPS VII mice using a recombinant adeno-associated virus

Watson¹,

Sayles²,

Chen³

et al. 1998

Gene Ther

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Mucopolysaccharidosis type VII (MPS VII) is a lysosomalproduced low GUS activity in several tissues. This latter storage disease caused by a genetic deficiency of ␤-glucutreatment of MPS VII mice reduced glycosaminoglycan ronidase (GUS). We used a recombinant adeno-associalevels in the liver to normal and reduced storage granules ted virus vector (AAV-GUS) to deliver GUS cDNA to MPS dramatically. We show that a single administration of VII mice. The route of vector administration had a dramatic AAV-GUS can provide sustained expression of GUS in a effect on the extent and distribution of GUS activity. Intravariety of cell types and is sufficient to reverse the disease muscular injection of AAV-GUS resulted in high, localized phenotype at least in the liver. production of GUS, while intravenous administration

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“…22 -24 For the murine, canine, and feline models, the cDNA sequences are known, and the mutations have been identified. 22,25,26 Treatment of lysosomal storage diseases is based on crosscorrection; the ability of the normal enzyme to be taken up by deficient cells. 27 Intravenous delivery of recombinant adeno-associated virus (rAAV) vectors in MPS VII mice resulted in substantial correction of disease and included normalization or significant improvements of body growth, retinal morphology and function, auditory deficits, skeletal abnormalities, and lifespan with stable enzyme activity for at least 1 year post treatment.…”

Section: Canine Modelsmentioning

confidence: 99%

Large animal models and gene therapy

2005

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Over the last two decades, gene transfer experiments for the treatment of inherited or acquired diseases have mainly been performed in mice. While mice provide proof of principle and allow testing of a variety of therapeutic modalities, mouse models have some limitations, as only short-term experiments can be performed, their homogenous genetic background is unlike humans, and the knockout models do not always faithfully represent the human disease. Naturally occurring large animal models of human genetic diseases have become increasingly important despite the costs and the extensive clinical attention they require because of their similarities to human patients. Large animals are reasonably outbred, long lived allowing for longitudinal studies, are more similar in size to a neonate or small child providing an opportunity to address issues related to scaling up therapy, and many physiological parameters including the immune system are more similar to those in humans versus those in mice.

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A single-base-pair deletion in the beta-glucuronidase gene accounts for the phenotype of murine mucopolysaccharidosis type VII.

Cited by 119 publications

References 21 publications

Prevention of systemic clinical disease in MPS VII mice following AAV-mediated neonatal gene transfer

Prevention of systemic clinical disease in MPS VII mice following AAV-mediated neonatal gene transfer

Treatment of lysosomal storage disease in MPS VII mice using a recombinant adeno-associated virus

Large animal models and gene therapy

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