title: Decreased performance in IDUA knockout mouse mimic limitations of joint function and locomotion in patients with Hurler syndrome.
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.
authors.affiliation: Clinical Research Center, Samsung Biomedical Research Institute, Seoul, Republic of Korea.|Present Address: MOGAM Biotechnology Institute, Yongin, Republic of Korea.
authors.forename: Chihwa
authors.initials: C
authors.lastname: Kim
authors.affiliation: Department of Pediatrics, Pusan National University Hospital, Pusan National University School of Medicine, Busan, Republic of Korea.
authors.forename: Min Jung
authors.initials: MJ
authors.lastname: Kwak
authors.affiliation: Department of Pediatrics, Samsung Medical Center, Sungkyunkwan University School of Medicine, 81 Irwon-ro, Gangnam-gu, Seoul, 135-710, Republic of Korea.
authors.forename: Sung Yoon
authors.initials: SY
authors.lastname: Cho
authors.affiliation: Clinical Research Center, Samsung Biomedical Research Institute, Seoul, Republic of Korea.
authors.forename: Ah-Ra
authors.initials: AR
authors.lastname: Ko
authors.affiliation: Samsung Biomedical Research Institute, Samsung Advanced Institute of Technology, Seoul, Republic of Korea.
authors.forename: Jinguen
authors.initials: J
authors.lastname: Rheey
authors.affiliation: Department of Physical and Rehabilitation Medicine, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea.
authors.forename: Jeong-Yi
authors.initials: JY
authors.lastname: Kwon
authors.affiliation: Department of Molecular Science and Technology, Ajou University, Suwon, Republic of Korea.
authors.forename: Yokyung
authors.initials: Y
authors.lastname: Chung
authors.affiliation: Department of Pediatrics, Samsung Medical Center, Sungkyunkwan University School of Medicine, 81 Irwon-ro, Gangnam-gu, Seoul, 135-710, Republic of Korea. jindk@skku.edu.
authors.forename: Dong-Kyu
authors.initials: DK
authors.lastname: Jin
mesh_terms: D000818:Animals; D005260:Female; D018737:Hand Strength / Q000502:physiology; D006801:Humans; D007068:Iduronidase / Q000172:deficiency* / Q000235:genetics; D007592:Joint Diseases / Q000000981:diagnostic imaging* / Q000201:enzymology* / Q000235:genetics; D008124:Locomotion / Q000502:physiology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008059:Mucopolysaccharidosis I / Q000000981:diagnostic imaging* / Q000201:enzymology* / Q000235:genetics; D011859:Radiography
chemical_list: D007068:Iduronidase