A mutation in synaptojanin 2 causes progressive hearing loss in the ENU-mutagenised mouse strain Mozart.
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 i...
| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2011-03-01
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| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC3057978?pdf=render |
| _version_ | 1819102657937145856 |
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| author | Shehnaaz S M Manji Louise H Williams Kerry A Miller Lisa M Ooms Melanie Bahlo Christina A Mitchell Hans-Henrik M Dahl |
| author_facet | Shehnaaz S M Manji Louise H Williams Kerry A Miller Lisa M Ooms Melanie Bahlo Christina A Mitchell Hans-Henrik M Dahl |
| author_sort | Shehnaaz S M Manji |
| collection | DOAJ |
| description | 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.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.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. |
| first_indexed | 2024-12-22T01:38:03Z |
| format | Article |
| id | doaj.art-66b3bb9bee1a448193c836fec6c9afef |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-22T01:38:03Z |
| publishDate | 2011-03-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-66b3bb9bee1a448193c836fec6c9afef2022-12-21T18:43:18ZengPublic Library of Science (PLoS)PLoS ONE1932-62032011-03-0163e1760710.1371/journal.pone.0017607A mutation in synaptojanin 2 causes progressive hearing loss in the ENU-mutagenised mouse strain Mozart.Shehnaaz S M ManjiLouise H WilliamsKerry A MillerLisa M OomsMelanie BahloChristina A MitchellHans-Henrik M DahlHearing 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.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.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.http://europepmc.org/articles/PMC3057978?pdf=render |
| spellingShingle | Shehnaaz S M Manji Louise H Williams Kerry A Miller Lisa M Ooms Melanie Bahlo Christina A Mitchell Hans-Henrik M Dahl A mutation in synaptojanin 2 causes progressive hearing loss in the ENU-mutagenised mouse strain Mozart. PLoS ONE |
| title | A mutation in synaptojanin 2 causes progressive hearing loss in the ENU-mutagenised mouse strain Mozart. |
| title_full | A mutation in synaptojanin 2 causes progressive hearing loss in the ENU-mutagenised mouse strain Mozart. |
| title_fullStr | A mutation in synaptojanin 2 causes progressive hearing loss in the ENU-mutagenised mouse strain Mozart. |
| title_full_unstemmed | A mutation in synaptojanin 2 causes progressive hearing loss in the ENU-mutagenised mouse strain Mozart. |
| title_short | A mutation in synaptojanin 2 causes progressive hearing loss in the ENU-mutagenised mouse strain Mozart. |
| title_sort | mutation in synaptojanin 2 causes progressive hearing loss in the enu mutagenised mouse strain mozart |
| url | http://europepmc.org/articles/PMC3057978?pdf=render |
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