Adenomatous Polyposis Coli Protein (APC) Is Required for Normal Hearing

HICKMAN, T; GOMEZ CASATI, ME; CORFAS G; JACOB, M

Congreso; The Association for Research in Otolaryngology, midwinter meeting; 2011

While originally believed to function mostly as a tumor suppressor protein, adenomatous polyposis coli (APC) has recently been found to play a critical role in neuronal development. APC functions to promote polarization, direct axon outgrowth and enhance synapse assembly and maturation. Moreover, studies in migrating fibroblasts show that APC interacts with fragile X mental retardation protein (FMRP) and is required for localizing selected mRNAs at sites of local translation. The critical role of APC in neurons is further supported by the association of mental retardation and autism with APC gene mutations in humans. Despite APC’s importance for proper development, its role in the cochlea has yet to be defined. Our preliminary studies show that APC is concentrated at (9/10-nAChR-containing efferent olivocochlear synapses of sensory hair cells. In addition to nicotinic synapses, APC is also enriched at glutamatergic synapses, suggesting a role at spiral ganglion neuron contacts with inner hair cells.. To define APC’s role in the cochlea, we have characterized the auditory phenotype of our APC conditional knock-out mouse. We find abnormal auditory brainstem responses (ABRs) and distortion product otoacoustic emissions (DPOAEs) compared to control littermates. The molecular organization of auditory synapses is also altered in the APC cKO mouse. Our findings suggest that APC expression is necessary for cochlear development and normal hearing.