Inner ear pathology in the mucopolysaccharidosis VII mouse

• Published in: Hearing research Vol. 169; no. 1; pp. 69 - 84
• Main Authors: Ohlemiller, Kevin K, Hennig, Anne K, Lett, Jaclynn M, Heidbreder, Arnold F, Sands, Mark S
• Format: Journal Article
• Language: English
• Published: Amsterdam Elsevier B.V 01.07.2002; Elsevier
• Subjects: Action Potentials; Animals; Auditory Threshold; Biological and medical sciences; Carbohydrates (enzymatic deficiencies). Glycogenosis; Cell Count; Cochlea; Crista; Disease Models, Animal; Ear, Inner - pathology; Errors of metabolism; Evoked Potentials, Auditory, Brain Stem; Female; Glucuronidase - genetics; Glucuronidase - metabolism; Hair cell; Hair Cells, Auditory - pathology; Hearing Loss, Conductive - genetics; Hearing Loss, Conductive - pathology; Hearing Loss, Conductive - physiopathology; Hearing Loss, Sensorineural - genetics; Hearing Loss, Sensorineural - pathology; Hearing Loss, Sensorineural - physiopathology; Humans; Lysosomal storage disease; Macula; Male; Medical sciences; Metabolic diseases; Mice; Mice, Mutant Strains; Mucopolysaccharidosis VII - genetics; Mucopolysaccharidosis VII - pathology; Mucopolysaccharidosis VII - physiopathology; Sly syndrome; β-Glucuronidase; Macula; β-Glucuronidase; Cochlea; GAG, glycosaminoglycan; Hair cell; MPS VII, mucopolysaccharidosis type VII; Crista; Lysosomal storage disease; Sly syndrome; CAPTC, compound action potential tuning curve; Diseases of the osteoarticular system; Auditory disorder; Mucopolysaccharidosis; Enzymopathy; ENT disease; Carbohydrate; Vestibular system; Hair cell of the ear; Enzyme; Internal ear disease; Rodentia; Metabolic diseases; Genetic disease; Vertebrata; Mammalia; Mouse; Glycosidases; Animal; Hydrolases; O-Glycosidases; Sensory hearing loss
• ISSN: 0378-5955; 1878-5891
• DOI: 10.1016/S0378-5955(02)00341-6

Mucopolysaccharidosis type VII (MPS VII, Sly syndrome) is caused by dysfunction of the acid hydrolase β- D-glucuronidase. The defect results in the accumulation of incompletely degraded glycosaminoglycans within lysosomes of a wide array of cell types. MPS VII is associated with mixed (conductive and sensorineural) hearing loss, vision defects, shortened stature, mental retardation and decreased lifespan. Whether the sensorineural component of hearing loss in MPS VII involves degeneration of cochlear sensory cells is not yet clear. The MPS VII mouse resembles its human counterpart in all major aspects, and has been the focus of extensive research seeking to correct MPS VII and other lysosomal storage diseases. The value of potential treatments for this hearing loss can be determined only if cochlear pathology in this model is well characterized. We examined threshold sensitivity, frequency tuning, hair cell density and the appearance of the cochlea and vestibular organs in MPS VII mice ranging from 1.0 to 7.5 months of age. At all ages, lysosomal storage is pronounced within cells of spiral limbus, spiral prominence, spiral ligament and glial cells, but not within organ of Corti, stria vascularis, or neurons. Within the vestibular maculae and cristae, both hair cells and supporting cells also show lysosomal storage. Although hearing thresholds are never normal, reduction in the sharpness of frequency tuning is not apparent until 2.5 months of age, suggesting that the sensorineural component of hearing loss begins in adulthood. No evidence was found for cell loss within the organ of Corti, or any other structure, however. Our results suggest that sensorineural hearing loss in the MPS VII mouse is not caused by degeneration, but may arise from alterations in mass and stiffness of cochlear structures or impaired sensory cell function. They also indicate a possible vestibular component in MPS VII.