The Gunn Rat: An Experimental Model for Central Deafness

Abstract

The Gunn rat which develops neonatal hyperbilirubinemia has been used as an experimental model to evaluate the effect of bilirubin on the auditory system. Electrocochleographic and morphological studies (including light microscopy, surface preparations and transmission electron microscopy) did not reveal any cochlear abnormality in homozygous Gunn rats. Brainstem auditory evoked potentials showed morphological and amplitude changes suggesting a functional damage in the brainstem auditory pathways. These results suggest that hearing loss, when observed in kernicterus, is primarily due to neuronal damage at the level of brainstem auditory nuclei.

Bilirubin and the Auditory System

“…These findings are in agreement with previous histologic studies on Gunn rats. 5,6 ABR Studies in the Gunn Rat The pathologic findings correspond to abnormalities of the ABR in jaundiced Gunn rats that we have previously reported. There are differences in ABR wave latencies and amplitudes in jaundiced Gunn rats during development and in adulthood.…”

“…Kernicterus does not affect the inner ear, either in humans 3,4 or in Gunn rats. 5,6 Audiometric findings in humans generally show bilateral highfrequency symmetric sensory neural hearing loss with recruitment. 7 Recruitment or abnormal loudness growth functions are also found.…”

Auditory neuropathy — neural and synaptic mechanisms

“…The precise disease mechanisms of bilirubin neurotoxicity are not yet well understood. The jaundiced Gunn rat that carries a mutation in the gene encoding UDPglucuronosyltransferase 1 is an animal model for human hyperbilirubinaemia 105 . Moreover, application of bilirubin has been used to study acute effects of bilirubinaemia 106 .…”

Cochlear Implantation in Auditory Neuropathy Spectrum Disorder

“…The Gunn rat pup provides a model of the effects of kernicterus in the neonate. Electrophysiological and anatomical studies have shown that severe cases of kernicterus in the Gunn rat lead to disruption of the auditory pathway from the cochlear nucleus to the higher auditory brainstem, including the inferior colliculus (Uziel et al, 1983). While both inner and outer hair cells appear to be spared by high levels of bilirubin, the spiral ganglion cells of auditory neurones can be disrupted (Shapiro, 2005), indicating a neuronal cause of ANSD.…”