Mouse screen reveals multiple new genes underlying mouse and human hearing loss

TY - JOUR

T1 - Mouse screen reveals multiple new genes underlying mouse and human hearing loss

AU - Ingham, Neil J.

AU - Pearson, Selina A.

AU - Vancollie, Valerie E

AU - Lewis, Morag Ann

AU - Chen, Jing

AU - Buniello, Annalisa

AU - Martelletti, Elisa

AU - Steel, Karen

PY - 2019/4/11

Y1 - 2019/4/11

N2 - Adult-onset hearing loss is very common but we know little about the underlying molecular pathogenesis, impeding development of therapies. We took a genetic approach to identify new molecules involved in hearing loss by screening a large cohort of newly-generated mouse mutants using a sensitive electrophysiological test, the auditory brainstem response. We review here the findings from this screen. Thirty-eight unexpected genes associated with raised thresholds were detected from our unbiased sample of 1,211 genes tested, suggesting extreme genetic heterogeneity. A wide range of auditory pathophysiologies was found, and some mutant lines showed normal development followed by deterioration of responses, revealing new molecular pathways involved in progressive hearing loss. Several of the genes were associated with the range of hearing thresholds in the human population and one, SPNS2, was involved in childhood deafness. The new pathways required for maintenance of hearing discovered by this screen present new therapeutic opportunities.

AB - Adult-onset hearing loss is very common but we know little about the underlying molecular pathogenesis, impeding development of therapies. We took a genetic approach to identify new molecules involved in hearing loss by screening a large cohort of newly-generated mouse mutants using a sensitive electrophysiological test, the auditory brainstem response. We review here the findings from this screen. Thirty-eight unexpected genes associated with raised thresholds were detected from our unbiased sample of 1,211 genes tested, suggesting extreme genetic heterogeneity. A wide range of auditory pathophysiologies was found, and some mutant lines showed normal development followed by deterioration of responses, revealing new molecular pathways involved in progressive hearing loss. Several of the genes were associated with the range of hearing thresholds in the human population and one, SPNS2, was involved in childhood deafness. The new pathways required for maintenance of hearing discovered by this screen present new therapeutic opportunities.

KW - Common human disease

KW - Hearing impairment

KW - Genetic deafness

KW - Progressive hearing loss

KW - Mouse mutant screen

KW - Auditory Brainstem Response

KW - SPNS2

KW - Therapeutic opportunities

KW - Lipids in deafness

KW - Genetic heterogeneity

KW - Auditory pathology

UR - https://www.scopus.com/record/display.uri?eid=2-s2.0-85064814085&origin=SingleRecordEmailAlert&dgcid=raven_sc_search_en_us_email&txGid=39a58fde783ad7ba75f12cb6328b4b33

U2 - 10.1371/journal.pbio.3000194

DO - 10.1371/journal.pbio.3000194

M3 - Article

VL - 17

JO - PLoS biology

JF - PLoS biology

IS - 4

M1 - e3000194

ER -