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

Neil J Ingham; Selina A Pearson; Valerie E Vancollie; Victoria Rook; Morag A Lewis; Jing Chen; Annalisa Buniello; Elisa Martelletti; Lorenzo Preite; Chi Chung Lam; Felix D Weiss; Zӧe Powis; Pim Suwannarat; Christopher J Lelliott; Sally J Dawson; Jacqueline K White; Karen P Steel

doi:10.1371/journal.pbio.3000194

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

Neil J Ingham, Selina A Pearson, Valerie E Vancollie, Victoria Rook, Morag A Lewis, Jing Chen, Annalisa Buniello, Elisa Martelletti, Lorenzo Preite, Chi Chung Lam, Felix D Weiss, Zӧe Powis, Pim Suwannarat, Christopher J Lelliott, Sally J Dawson, Jacqueline K White, Karen P Steel

Wellcome Trust Sanger Institute; European Bioinformatics Institute
Health Psychology Section, Psychology Department, Institute of Psychology, Psychiatry and Neuroscience, King's College London, United Kingdom.
1Department of Hepatology, Imperial College London, London, UK. 2Institute of Liver Studies at King's College School of Medicine at King's College Hospital, London, UK. 3Institute of Human Health and Performance, University College London, London, UK. 4Department of Asthma Allergy and Lung Biology, King's College London, London, UK. 5Division of Critical Care Medicine, University of Alberta, Edmonton, Canada.
Boston University
Mid-Atlantic Permanente Medical Group
Univ London, Birkbeck University London, University College London, University of London Royal Veterinary College, University of London, St Georges University London, Imperial College London, Kings College London, Royal Holloway University London, Queen Mary University London, Div Populat Hlth Sci & Educ

Research output: Contribution to journal › Article › peer-review

Abstract

Adult-onset hearing loss is very common, but we know little about the underlying molecular pathogenesis impeding the 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 (ABR). 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.

Original language	English
Pages (from-to)	e3000194
Journal	PLoS Biology
Volume	17
Issue number	4
DOIs	https://doi.org/10.1371/journal.pbio.3000194
Publication status	Published - Apr 2019

Keywords

Acoustic Stimulation/methods
Adult
Animals
Anion Transport Proteins/genetics
Auditory Perception/genetics
Child
Electrophysiological Phenomena/genetics
Evoked Potentials, Auditory, Brain Stem/genetics
Female
Genetic Association Studies
Hearing/genetics
Hearing Loss/genetics
Humans
Male
Mice
Mice, Inbred C57BL

Access to Document

10.1371/journal.pbio.3000194

Cite this

Ingham, N. J., Pearson, S. A., Vancollie, V. E., Rook, V., Lewis, M. A., Chen, J., Buniello, A., Martelletti, E., Preite, L., Lam, C. C., Weiss, F. D., Powis, Z., Suwannarat, P., Lelliott, C. J., Dawson, S. J., White, J. K., & Steel, K. P. (2019). Mouse screen reveals multiple new genes underlying mouse and human hearing loss. PLoS Biology, 17(4), e3000194. https://doi.org/10.1371/journal.pbio.3000194

@article{0f2dd5e6d02d4a7ab5dac8ecabce22ed,

title = "Mouse screen reveals multiple new genes underlying mouse and human hearing loss",

abstract = "Adult-onset hearing loss is very common, but we know little about the underlying molecular pathogenesis impeding the 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 (ABR). 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.",

keywords = "Acoustic Stimulation/methods, Adult, Animals, Anion Transport Proteins/genetics, Auditory Perception/genetics, Child, Electrophysiological Phenomena/genetics, Evoked Potentials, Auditory, Brain Stem/genetics, Female, Genetic Association Studies, Hearing/genetics, Hearing Loss/genetics, Humans, Male, Mice, Mice, Inbred C57BL",

author = "Ingham, {Neil J} and Pearson, {Selina A} and Vancollie, {Valerie E} and Victoria Rook and Lewis, {Morag A} and Jing Chen and Annalisa Buniello and Elisa Martelletti and Lorenzo Preite and Lam, {Chi Chung} and Weiss, {Felix D} and Zӧe Powis and Pim Suwannarat and Lelliott, {Christopher J} and Dawson, {Sally J} and White, {Jacqueline K} and Steel, {Karen P}",

year = "2019",

month = apr,

doi = "10.1371/journal.pbio.3000194",

language = "English",

volume = "17",

pages = "e3000194",

journal = "PLoS Biology",

issn = "1544-9173",

publisher = "Public Library of Science",

number = "4",

}

Ingham, NJ, Pearson, SA, Vancollie, VE, Rook, V , Lewis, MA , Chen, J , Buniello, A , Martelletti, E , Preite, L , Lam, CC, Weiss, FD, Powis, Z, Suwannarat, P, Lelliott, CJ, Dawson, SJ, White, JK & Steel, KP 2019, 'Mouse screen reveals multiple new genes underlying mouse and human hearing loss', PLoS Biology, vol. 17, no. 4, pp. e3000194. https://doi.org/10.1371/journal.pbio.3000194

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 - Rook, Victoria

AU - Lewis, Morag A

AU - Chen, Jing

AU - Buniello, Annalisa

AU - Martelletti, Elisa

AU - Preite, Lorenzo

AU - Lam, Chi Chung

AU - Weiss, Felix D

AU - Powis, Zӧe

AU - Suwannarat, Pim

AU - Lelliott, Christopher J

AU - Dawson, Sally J

AU - White, Jacqueline K

AU - Steel, Karen P

PY - 2019/4

Y1 - 2019/4

N2 - Adult-onset hearing loss is very common, but we know little about the underlying molecular pathogenesis impeding the 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 (ABR). 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 the 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 (ABR). 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 - Acoustic Stimulation/methods

KW - Adult

KW - Animals

KW - Anion Transport Proteins/genetics

KW - Auditory Perception/genetics

KW - Child

KW - Electrophysiological Phenomena/genetics

KW - Evoked Potentials, Auditory, Brain Stem/genetics

KW - Female

KW - Genetic Association Studies

KW - Hearing/genetics

KW - Hearing Loss/genetics

KW - Humans

KW - Male

KW - Mice

KW - Mice, Inbred C57BL

U2 - 10.1371/journal.pbio.3000194

DO - 10.1371/journal.pbio.3000194

M3 - Article

C2 - 30973865

SN - 1544-9173

VL - 17

SP - e3000194

JO - PLoS Biology

JF - PLoS Biology

IS - 4

ER -

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

Abstract

Keywords

Access to Document

Fingerprint

Cite this