University Library
  • Login
A gateway to Melbourne's research publications
Minerva Access is the University's Institutional Repository. It aims to collect, preserve, and showcase the intellectual output of staff and students of the University of Melbourne for a global audience.
View Item 
  • Minerva Access
  • Medicine, Dentistry & Health Sciences
  • Melbourne Medical School
  • Paediatrics (RCH)
  • Paediatrics (RCH) - Research Publications
  • View Item
  • Minerva Access
  • Medicine, Dentistry & Health Sciences
  • Melbourne Medical School
  • Paediatrics (RCH)
  • Paediatrics (RCH) - Research Publications
  • View Item
JavaScript is disabled for your browser. Some features of this site may not work without it.

    A Mutation in Synaptojanin 2 Causes Progressive Hearing Loss in the ENU-Mutagenised Mouse Strain Mozart

    Thumbnail
    Citations
    Scopus
    Web of Science
    Altmetric
    27
    24
    Author
    Manji, SSM; Williams, LH; Miller, KA; Ooms, LM; Bahlo, M; Mitchell, CA; Dahl, H-HM
    Date
    2011-03-15
    Source Title
    PLOS ONE
    Publisher
    PUBLIC LIBRARY SCIENCE
    University of Melbourne Author/s
    MANJI, SHEHNAAZ; DAHL, HANS-HENRIK; Bahlo, Melanie
    Affiliation
    Paediatrics Royal Children'S Hospital
    Metadata
    Show full item record
    Document Type
    Journal Article
    Citations
    Manji, 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.
    Access Status
    Access this item via the Open Access location
    URI
    http://hdl.handle.net/11343/29062
    DOI
    10.1371/journal.pone.0017607
    Open Access at PMC
    http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3057978
    Description

    C - Journal Articles

    Abstract
    BACKGROUND: 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.
    Keywords
    Genetics not elsewhere classified; Clinical Health (Organs; Diseases and Abnormal Conditions) not elsewhere classified

    Export Reference in RIS Format     

    Endnote

    • Click on "Export Reference in RIS Format" and choose "open with... Endnote".

    Refworks

    • Click on "Export Reference in RIS Format". Login to Refworks, go to References => Import References


    Collections
    • Minerva Elements Records [53039]
    • Paediatrics (RCH) - Research Publications [2390]
    Minerva AccessDepositing Your Work (for University of Melbourne Staff and Students)NewsFAQs

    BrowseCommunities & CollectionsBy Issue DateAuthorsTitlesSubjectsThis CollectionBy Issue DateAuthorsTitlesSubjects
    My AccountLoginRegister
    StatisticsMost Popular ItemsStatistics by CountryMost Popular Authors