Sensorineural hearing loss in insulin‐like growth factor I‐null mice: a new model of human deafness

Abstract

It has been reported that mutations in the gene encoding human insulin-like growth factor-I (IGF-I) cause syndromic hearing loss. To study the precise role of IGF-I in auditory function and to hypothesize the possible morphological and electrophysiological changes that may occur in the human inner ear, we have analysed the auditory brainstem response in a mouse model of IGF-I deficiency. We show here that homozygous Igf-1(-/-) mice present an all-frequency involved bilateral sensorineural hearing loss. Igf-1(-/-) mice also present a delayed response to acoustic stimuli; this increases along the auditory pathway, indicating a contribution of the central nervous system to the hearing loss in Igf-1(-/-) mice. These results support the use of the Igf-1(-/-) mouse as a new model for the study of human syndromic deafness.

Genetic disorders in the GH–IGF-I axis in mouse and man

“…Auditory brainstem responses were analyzed S18 M J E Walenkamp and J M Wit in IGF-I K / K mice, showing an all-frequency involved bilateral sensorineural hearing loss. The delayed response to acoustic stimuli along the auditory pathway indicates the contribution of the CNS to the hearing loss in IGF-I deficiency (81). At a cellular level, a significant decrease in number and size of auditory neurons, increased apoptosis of cochlear neurons, a significant reduced volume of the cochlea and cochlear ganglion can result in abnormal differentiation and maturation of the cochlear ganglion cells and abnormal innervation of the sensory cells in the organ of Corti (82).…”

Insulin Receptor Substrate 2 (IRS2)-Deficient Mice Show Sensorineural Hearing Loss That Is Delayed by Concomitant Protein Tyrosine Phosphatase 1B (PTP1B) Loss of Function

“…Given the similar neural phenotype of both Igf1-and Irs2-null mice, we hypothesized that lack of IRS2 could also lead to hearing impairment in the same way as it happens in Igf1 -/-mice (14,19 …”

“…Hearing was evaluated by studying the auditory brainstem response (ABR) following standard methods (19,20). Click and 8-to 40-kHz tone burst stimuli were generated with SigGenRP™ software (Tucker-Davis Technologies, Alachua, FL, USA) and presented from 90 to 20 decibel sound pressure level (dB SPL) in 5-10 dB SPL steps.…”

“…Click and 8-to 40-kHz tone burst stimuli were generated with SigGenRP™ software (Tucker-Davis Technologies, Alachua, FL, USA) and presented from 90 to 20 decibel sound pressure level (dB SPL) in 5-10 dB SPL steps. The electrical response was amplified, recorded and averaged, and hearing thresholds were determined for each stimulus as described (19). Peak and interpeak latencies were analyzed at 90 dB SPL after click stimulation.…”

“…Similarly, Igf1 -/-mice exhibit delayed myelination (17,18), severe sensorineural deafness (19,20) and progressive blindness (21). The cochlea of IGF-1-deficient mice presents an abnormal tectorial membrane, increased neuronal apoptosis, poor myelination of nerve fibers (22,23) and impaired activation of protein kinase B (PKB; AKT) and rapid accelerated fibrosarcoma (RAF) kinases (24).…”