Paediatrics (RCH) - Research Publications

Permanent URI for this collection

http://hdl.handle.net/11343/199

Filters

2011 2
2
Reset filters

Settings
Statistics
Citations
Start date: 2000 × Subject: Diseases and Abnormal Conditions) not elsewhere classified ×

Search Results

Now showing 1 - 2 of 2
  • Item
    Thumbnail Image
    An X-traordinary stroke
    Verma, S ; Lewis, D ; Warne, G ; Grossmann, M (ELSEVIER SCIENCE INC, 2011-04-09)
  • Item
    Thumbnail Image
    A Mutation in Synaptojanin 2 Causes Progressive Hearing Loss in the ENU-Mutagenised Mouse Strain Mozart
    Manji, SSM ; Williams, LH ; Miller, KA ; Ooms, LM ; Bahlo, M ; Mitchell, CA ; Dahl, H-HM ; Krahe, R (PUBLIC LIBRARY SCIENCE, 2011-03-15)
    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.