Hearing function and ossicular deformities and fractures in the oim mouse model of brittle bone disease

Abstract

Hearing loss is a prevalent symptom of osteogenesis imperfecta (OI), a group of collagen type I-related skeletal disorders, commonly known as brittle bone disease. Clinical manifestation of hearing loss in OI often presents with stapes footplate fixation and hypodense foci in the otic capsule. However, the etiology and evolution of OI-hearing loss and its relation to bone abnormalities are still unknown. This study investigates the onset, severity, and progression of hearing loss in the homozygous oim mouse model of severe OI Type III, which is reported to exhibit hearing loss at 11-12 weeks of age (Chen et al., 2007), using auditory brainstem responses up to 26 weeks of age. We further examine the presence of deformities, microcracks, and fractures of the ossicular chain using synchrotron microtomography. Our results demonstrate that oim/oim mice have normal hearing, regardless of i) their parental lineage, ii) their husbandry in isolation or with other animals, iii) their mastication with powder or chow food, and iv) their anesthesia with single or multiple ketamine injections. Bone abnormalities like excessive formations, fusions, and fractures, were observed in up to 33 % of wild-type and up to 43 % of oim/oim mice in each group. Among these, joint and bone-tendon abnormalities were twice as frequent in the oim/oim mice compared to the wild-type mice. Notably, these abnormalities did not impact the hearing response in mice. Whether such bone abnormalities occur and alter auditory function in humans with OI remains uncertain.