The IMPC is hunting unknown genes responsible for hearing loss by screening knockout mice
- 360 million people worldwide live with mild to profound hearing loss
- 70% hearing loss occurs as an isolated condition (non-syndromic) and 30% with additional phenotypes (syndromic)
- The vast majority of genes responsible for hearing loss are unknown
In order to identify the function of genes, the consortium uses a series of standardised protocols as described in IMPReSS (International Mouse Phenotyping Resource of Standardised Screens).
Hearing capacity is assessed using an Auditory Brain Stem response (ABR) test conducted at 14 weeks of age. Hearing is assessed at five frequencies – 6kHz, 12kHz, 18kHz, 24kHz and 30kHz – as well as a broadband click stimulus. Increased thresholds are indicative of abnormal hearing. Abnormalities in adult ear morphology are recorded as part of the Combined SHIRPA and Dysmorphology (CSD) protocol, which includes a response to a click box test (absence is indicative of a strong hearing deficit) and visual inspection for behavioural signs that may indicate vestibular dysfunction e.g. head bobbing or circling.
Procedures that can lead to relevant phenotype associations
IMPC Deafness Publication
Hearing loss investigated in 3,006 knockout mouse lines
- 67 genes identified as candidate hearing loss genes
- 52 genes are not previously associated with hearing loss and encompass a wide range of functions from structural proteins to transcription factors
- Among the novel candidate genes, Atp2b1 is expressed in the inner ear and Sema3f plays a role in sensory hair cell innervation in the cochlea
- The IMPC will continue screening for hearing loss mutants in its second 5 year phase
Response data from the Auditory Brain Stem response (ABR) test was used – hearing at five frequencies, 6kHz, 12kHz, 18kHz, 24kHz and 30kHz was measured.
- Control wildtype mice from each phenotypic centre included, matched for gender, age, phenotypic pipeline and metadata (e.g. instrument)
- Our production statistical approach that automatically detects mutants with abnormal hearing was manually curated to yield 67 genes with profound hearing loss
Sixty-seven deafness genes were identified:
|Gene symbol||Zygosity||Status||Hearing loss|