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dc.contributor.authorManji, SSM
dc.contributor.authorWilliams, LH
dc.contributor.authorMiller, KA
dc.contributor.authorOoms, LM
dc.contributor.authorBahlo, M
dc.contributor.authorMitchell, CA
dc.contributor.authorDahl, H-HM
dc.date.available2014-05-21T22:28:43Z
dc.date.available2011-01-30
dc.date.available2011-01-30
dc.date.available2011-01-30
dc.date.available2011-01-30
dc.date.issued2011-03-15
dc.identifierhttp://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000288513900013&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=d4d813f4571fa7d6246bdc0dfeca3a1c
dc.identifierARTN e17607
dc.identifier.citationManji, S. S. M., Williams, L. H., Miller, K. A., Ooms, L. M., Bahlo, M., Mitchell, C. A. & Dahl, H. -H. M. (2011). A Mutation in Synaptojanin 2 Causes Progressive Hearing Loss in the ENU-Mutagenised Mouse Strain Mozart. PLOS ONE, 6 (3), https://doi.org/10.1371/journal.pone.0017607.
dc.identifier.issn1932-6203
dc.identifier.urihttp://hdl.handle.net/11343/29062
dc.descriptionC - Journal Articles
dc.description.abstractBACKGROUND: Hearing impairment is the most common sensory impairment in humans, affecting 1:1,000 births. We have identified an ENU generated mouse mutant, Mozart, with recessively inherited, non-syndromic progressive hearing loss caused by a mutation in the synaptojanin 2 (Synj2), a central regulatory enzyme in the phosphoinositide-signaling cascade. METHODOLOGY/PRINCIPAL FINDINGS: The hearing loss in Mozart is caused by a p.Asn538Lys mutation in the catalytic domain of the inositol polyphosphate 5-phosphatase synaptojanin 2. Within the cochlea, Synj2 mRNA expression was detected in the inner and outer hair cells but not in the spiral ganglion. Synj2(N538K) mutant protein showed loss of lipid phosphatase activity, and was unable to degrade phosphoinositide signaling molecules. Mutant Mozart mice (Synj2(N538K/N538K)) exhibited progressive hearing loss and showed signs of hair cell degeneration as early as two weeks of age, with fusion of stereocilia followed by complete loss of hair bundles and ultimately loss of hair cells. No changes in vestibular or neurological function, or other clinical or behavioral manifestations were apparent. CONCLUSIONS/SIGNIFICANCE: Phosphoinositides are membrane associated signaling molecules that regulate many cellular processes including cell death, proliferation, actin polymerization and ion channel activity. These results reveal Synj2 as a critical regulator of hair cell survival that is essential for hair cell maintenance and hearing function.
dc.languageEnglish
dc.publisherPUBLIC LIBRARY SCIENCE
dc.subjectGenetics not elsewhere classified; Clinical Health (Organs
dc.subjectDiseases and Abnormal Conditions) not elsewhere classified
dc.titleA Mutation in Synaptojanin 2 Causes Progressive Hearing Loss in the ENU-Mutagenised Mouse Strain Mozart
dc.typeJournal Article
dc.identifier.doi10.1371/journal.pone.0017607
melbourne.affiliationThe University of Melbourne
melbourne.affiliation.departmentPaediatrics Royal Children'S Hospital
melbourne.source.titlePLOS ONE
melbourne.source.volume6
melbourne.source.issue3
dc.research.codefor060499
dc.research.codeseo2008920199
dc.rights.licenseCC BY
melbourne.publicationid159694
melbourne.elementsid332364
melbourne.openaccess.pmchttp://www.ncbi.nlm.nih.gov/pmc/articles/PMC3057978
melbourne.contributor.authorMANJI, SHEHNAAZ
melbourne.contributor.authorDAHL, HANS-HENRIK
melbourne.contributor.authorBahlo, Melanie
dc.identifier.eissn1932-6203
pubs.acceptance.date2011-01-30
melbourne.accessrightsAccess this item via the Open Access location


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