Targeted Disruption of Mouse Coch Provides Functional Evidence That DFNA9 Hearing Loss is Not a COCH Haploinsufficiency Disorder

Overview

Journal Hum Genet

Specialty Genetics

Date 2005 Aug 4

PMID 16078052

Citations 17

Authors

Tomoko Makishima

Clara I Rodriguez

Nahid G Robertson

Cynthia C Morton

Colin L Stewart

Andrew J Griffith

Affiliations

Soon will be listed here.

Abstract

Dominant progressive hearing loss and vestibular dysfunction DFNA9 is caused by mutations of the human COCH gene. COCH encodes cochlin, a highly abundant secreted protein of unknown function in the inner ear. Cochlin has an N-terminal LCCL domain followed by two vWA domains, and all known DFNA9 mutations are either missense substitutions or an amino acid deletion in the LCCL domain. Here, we have characterized the auditory phenotype associated with a genomic deletion of mouse Coch downstream of the LCCL domain. Homozygous Coch (-/-) mice express no detectable cochlin in the inner ear. Auditory brainstem responses to click and pure-tone stimuli (8, 16, 32 kHz) were indistinguishable among wild type and homozygous Coch (-/-) mice. A Coch-LacZDeltaneo reporter allele detected Coch mRNA expression in nonsensory epithelial and stromal regions of the cochlea and vestibular labyrinth. These data provide functional evidence that DFNA9 is probably not caused by COCH haploinsufficiency, but via a dominant negative or gain-of-function effect, in nonsensory regions of the inner ear.

Citing Articles

Auditory function analysis in immunodeficient STAT1 knock-out mice: Considerations for viral infection models.

Suzuki T, Maruyama J, Cook R, Urata S, Paessler S, Makishima T Neurosci Lett. 2020; 740:135427.

PMID: 33069812 PMC: 7708419. DOI: 10.1016/j.neulet.2020.135427.

Novel loss-of-function mutations in COCH cause autosomal recessive nonsyndromic hearing loss.

Booth K, Ghaffar A, Rashid M, Hovey L, Hussain M, Frees K Hum Genet. 2020; 139(12):1565-1574.

PMID: 32562050 PMC: 7572817. DOI: 10.1007/s00439-020-02197-5.

The use of nonhuman primates in studies of noise injury and treatment.

Burton J, Valero M, Hackett T, Ramachandran R J Acoust Soc Am. 2019; 146(5):3770.

PMID: 31795680 PMC: 6881191. DOI: 10.1121/1.5132709.

Cochlear histopathology in human genetic hearing loss: State of the science and future prospects.

Bommakanti K, Iyer J, Stankovic K Hear Res. 2019; 382:107785.

PMID: 31493568 PMC: 6778517. DOI: 10.1016/j.heares.2019.107785.

Genes important for otoneurological diagnostic purposes - current status and future prospects.

Pawlak-Osinska K, Linkowska K, Grzybowski T Acta Otorhinolaryngol Ital. 2018; 38(3):242-250.

PMID: 29984802 PMC: 6036948. DOI: 10.14639/0392-100X-1692.

References

de Kok Y, Bom S, Brunt T, Kemperman M, van Beusekom E, Robertson N . A Pro51Ser mutation in the COCH gene is associated with late onset autosomal dominant progressive sensorineural hearing loss with vestibular defects. Hum Mol Genet. 1999; 8(2):361-6. DOI: 10.1093/hmg/8.2.361. View

Trexler M, Banyai L, Patthy L . The LCCL module. Eur J Biochem. 2000; 267(18):5751-7. DOI: 10.1046/j.1432-1327.2000.01641.x. View

Colombatti A, Bonaldo P . The superfamily of proteins with von Willebrand factor type A-like domains: one theme common to components of extracellular matrix, hemostasis, cellular adhesion, and defense mechanisms. Blood. 1991; 77(11):2305-15. View

Fransen E, Verstreken M, Bom S, Lemaire F, Kemperman M, de Kok Y . A common ancestor for COCH related cochleovestibular (DFNA9) patients in Belgium and The Netherlands bearing the P51S mutation. J Med Genet. 2001; 38(1):61-5. PMC: 1734719. DOI: 10.1136/jmg.38.1.61. View

Ikezono T, Shindo S, Li L, Omori A, Ichinose S, Watanabe A . Identification of a novel Cochlin isoform in the perilymph: insights to Cochlin function and the pathogenesis of DFNA9. Biochem Biophys Res Commun. 2004; 314(2):440-6. DOI: 10.1016/j.bbrc.2003.12.106. View

Eavey R, Manolis E, Lubianca J, Merchant S, Seidman J, Seidman C . Mutations in COCH (formerly Coch5b2) cause DFNA9. Adv Otorhinolaryngol. 2000; 56:101-2. DOI: 10.1159/000059070. View

Robertson N, Resendes B, Lin J, Lee C, Aster J, Adams J . Inner ear localization of mRNA and protein products of COCH, mutated in the sensorineural deafness and vestibular disorder, DFNA9. Hum Mol Genet. 2001; 10(22):2493-500. DOI: 10.1093/hmg/10.22.2493. View

Merchant S, Linthicum F, Nadol Jr J . Histopathology of the inner ear in DFNA9. Adv Otorhinolaryngol. 2000; 56:212-7. DOI: 10.1159/000059105. View

Bom S, Kemperman M, de Kok Y, Huygen P, Verhagen W, Cremers F . Progressive cochleovestibular impairment caused by a point mutation in the COCH gene at DFNA9. Laryngoscope. 1999; 109(9):1525-30. DOI: 10.1097/00005537-199909000-00031. View

10.

Verhagen W, Bom S, Huygen P, Fransen E, Van Camp G, Cremers C . Familial progressive vestibulocochlear dysfunction caused by a COCH mutation (DFNA9). Arch Neurol. 2000; 57(7):1045-7. DOI: 10.1001/archneur.57.7.1045. View

11.

Szymko-Bennett Y, Kurima K, Olsen B, Seegmiller R, Griffith A . Auditory function associated with Col11a1 haploinsufficiency in chondrodysplasia (cho) mice. Hear Res. 2003; 175(1-2):178-82. DOI: 10.1016/s0378-5955(02)00736-0. View

12.

Verstreken M, Declau F, Wuyts F, DHaese P, Van Camp G, Fransen E . Hereditary otovestibular dysfunction and Ménière's disease in a large Belgian family is caused by a missense mutation in the COCH gene. Otol Neurotol. 2001; 22(6):874-81. DOI: 10.1097/00129492-200111000-00028. View

13.

Liepinsh E, Trexler M, Kaikkonen A, Weigelt J, Banyai L, Patthy L . NMR structure of the LCCL domain and implications for DFNA9 deafness disorder. EMBO J. 2001; 20(19):5347-53. PMC: 125649. DOI: 10.1093/emboj/20.19.5347. View

14.

Robertson N, Lu L, Heller S, Merchant S, Eavey R, McKenna M . Mutations in a novel cochlear gene cause DFNA9, a human nonsyndromic deafness with vestibular dysfunction. Nat Genet. 1998; 20(3):299-303. DOI: 10.1038/3118. View

15.

Griffith A, Szymko Y, Kaneshige M, Quinonez R, Kaneshige K, Heintz K . Knock-in mouse model for resistance to thyroid hormone (RTH): an RTH mutation in the thyroid hormone receptor beta gene disrupts cochlear morphogenesis. J Assoc Res Otolaryngol. 2002; 3(3):279-88. PMC: 3202409. DOI: 10.1007/s101620010092. View

16.

Fransen E, Verstreken M, Verhagen W, Wuyts F, Huygen P, DHaese P . High prevalence of symptoms of Menière's disease in three families with a mutation in the COCH gene. Hum Mol Genet. 1999; 8(8):1425-9. DOI: 10.1093/hmg/8.8.1425. View

17.

Kamarinos M, McGill J, Lynch M, Dahl H . Identification of a novel COCH mutation, I109N, highlights the similar clinical features observed in DFNA9 families. Hum Mutat. 2001; 17(4):351. DOI: 10.1002/humu.37. View

18.

Colombatti A, Bonaldo P, Doliana R . Type A modules: interacting domains found in several non-fibrillar collagens and in other extracellular matrix proteins. Matrix. 1993; 13(4):297-306. DOI: 10.1016/s0934-8832(11)80025-9. View

19.

Khetarpal U . DFNA9 is a progressive audiovestibular dysfunction with a microfibrillar deposit in the inner ear. Laryngoscope. 2000; 110(8):1379-84. DOI: 10.1097/00005537-200008000-00030. View

20.

Usami S, Takahashi K, Yuge I, Ohtsuka A, Namba A, Abe S . Mutations in the COCH gene are a frequent cause of autosomal dominant progressive cochleo-vestibular dysfunction, but not of Meniere's disease. Eur J Hum Genet. 2003; 11(10):744-8. DOI: 10.1038/sj.ejhg.5201043. View