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Orphanet Journal of Rare Diseases

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Open Access 01-12-2015 | Research

Decreased performance in IDUA knockout mouse mimic limitations of joint function and locomotion in patients with Hurler syndrome

Authors: Chihwa Kim, Min Jung Kwak, Sung Yoon Cho, Ah-ra Ko, Jinguen Rheey, Jeong-Yi Kwon, Yokyung Chung, Dong-Kyu Jin

Published in: Orphanet Journal of Rare Diseases | Issue 1/2015

Abstract

Background

Mucopolysaccharidosis type I (MPS I) is caused by the deficiency of alpha-L-iduronidase (IDUA), which is involved in the degradation of glycosaminoglycans (GAGs), such as heparan sulfate and dermatan sulfate in the lysosome. It has been reported that joint symptoms are almost universal in MPS I patients, and even in the case of attenuated disease, they are the first symptom that brings a child to medical attention. However, functional tests and biological markers have not been published for the evaluation of the limitations in joint and locomotion in animal model-mimicking MPS.

Methods

We generated IDUA knockout (KO) mice to observe whether they present impairment of joint function. KO mice were characterized phenotypically and tested dual-energy X-ray absorptiometry analysis (DEXA), open-field, rotarod, and grip strength.

Results

The IDUA KO mice, generated by disruption between exon 6 and exon 9, exhibited clinical and laboratory findings, such as high urinary GAGs excretion, GAGs accumulation in various tissues, and significantly increased bone mineral density (BMD) in both female and male mice in the DEXA of the femur and whole bone. Remarkably, we observed a decrease in grasp function, decreased performance in the rotarod test, and hypo-activity in the open-field test, which mimic the limitations of joint mobility and decreased motor performance in the 6-min walk test in patients with MPS I.

Conclusions

We generated a new IDUA KO mouse, tested open field, rotarod and grip strength and demonstrated decrease in grip strength, decreased performance and hypo-activity, which may be useful for investigating therapeutic approaches, and studying the pathogenesis of joint and locomotion symptoms in MPS I.

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Title: Decreased performance in IDUA knockout mouse mimic limitations of joint function and locomotion in patients with Hurler syndrome
Authors: Chihwa Kim
Min Jung Kwak
Sung Yoon Cho
Ah-ra Ko
Jinguen Rheey
Jeong-Yi Kwon
Yokyung Chung
Dong-Kyu Jin
Publication date: 01-12-2015
Publisher: BioMed Central
Published in: Orphanet Journal of Rare Diseases / Issue 1/2015
Electronic ISSN: 1750-1172
DOI: https://doi.org/10.1186/s13023-015-0337-3

At a glance: The STEP trials

Springer Medicine

Decreased performance in IDUA knockout mouse mimic limitations of joint function and locomotion in patients with Hurler syndrome

Abstract

Background

Methods

Results

Conclusions

At a glance: The STEP trials

Springer Medicine

Abstract

Background

Methods

Results

Conclusions

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