Auditory characteristics and therapeutic effects of enzyme replacement in mouse model of the mucopolysaccharidosis (MPS) II

• Published in: American journal of medical genetics. Part A 2012-09, Vol.158A (9), p.2131-2138
• Main Authors: Hong, Sung Hwa, Chu, Hosuk, Kim, Ki Ryung, Ko, Moon Hee, Kwon, See Youn, Moon, Il Joon, Chung, Won-Ho, Cho, Yang-Sun, Kim, Chi-Hwa, Suh, Myung-Whan, Choi, Eun Wha, Sohn, Young Bae, Park, Sung Won, Kim, Se-Hwa, Cho, Sung-Yoon, Ko, Ah-Ra, Jin, Dong-Kyu
• Format: Article
• Language: English
• Subjects: Age; Animals; Auditory Pathways; Biological and medical sciences; Brain Stem - physiopathology; Carbohydrates (enzymatic deficiencies). Glycogenosis; Disease Models, Animal; Ear, Middle - diagnostic imaging; Ear, Middle - metabolism; enzyme replacement; Errors of metabolism; Glycosaminoglycans - metabolism; hearing; Hunter syndrome; Iduronate Sulfatase - therapeutic use; Medical genetics; Medical sciences; Metabolic diseases; Mice; Mice, Knockout; mouse model; MPS II; Mucopolysaccharidosis II - drug therapy; Mucopolysaccharidosis II - metabolism; Mucopolysaccharidosis II - physiopathology; Tomography, X-Ray Computed
• ISSN: 1552-4825; 1552-4833
• DOI: 10.1002/ajmg.a.35498

Mucopolysaccharidosis (MPS) II is an X‐linked metabolic disorder caused by dysfunction of iduronate‐2‐sulfatase (I2S). This abnormality causes the progressive accumulation of incompletely degraded glycosaminoglycans (GAGs) in the lysosomes. The auditory characteristics of MPS II in mouse models have not been reported. In this study, we evaluated the auditory characteristics of the MPS II in IDS knock‐out (IDS‐KO) mice. In addition, the effect of enzyme replacement therapy (ERT) on hearing was studied. The IDS‐KO mice had normal histology of the cochlea and retained good hearing at 7 weeks of age. However, at 17 weeks of age, the hearing thresholds of the IDS‐KO mice were elevated and exudates were found in the middle ear. The hearing thresholds of the enzyme‐treated IDS‐KO (IDS‐ERT) mice were similar to the wild‐type (WT) mice at 17 weeks. Moreover, the microstructure of the inner ear was similar to the IDS‐KO by transmission electron microscopy. The histology findings indicated that the microstructure of the inner ear was similar in comparisons between IDS‐KO and IDS‐ERT mice, even after 10 weeks of treatment. However, the hearing deficits in the MPS II mouse model can be prevented if ERT is started before the onset of hearing impairment. © 2012 Wiley Periodicals, Inc.