Prestin-Dependence of Outer Hair Cell Survival and Partial Rescue of Outer Hair Cell Loss in PrestinV499G/Y501H Knockin Mice.
A knockin (KI) mouse expressing mutated prestinV499G/Y501H (499 prestin) was created to study cochlear amplification. Recordings from isolated outer hair cells (OHC) in this mutant showed vastly reduced electromotility and, as a consequence, reduced hearing sensitivity. Although 499 prestin OHCs wer...
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2015-01-01
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| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC4684303?pdf=render |
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| author | Mary Ann Cheatham Roxanne M Edge Kazuaki Homma Emily L Leserman Peter Dallos Jing Zheng |
| author_facet | Mary Ann Cheatham Roxanne M Edge Kazuaki Homma Emily L Leserman Peter Dallos Jing Zheng |
| author_sort | Mary Ann Cheatham |
| collection | DOAJ |
| description | A knockin (KI) mouse expressing mutated prestinV499G/Y501H (499 prestin) was created to study cochlear amplification. Recordings from isolated outer hair cells (OHC) in this mutant showed vastly reduced electromotility and, as a consequence, reduced hearing sensitivity. Although 499 prestin OHCs were normal in stiffness and longer than OHCs lacking prestin, accelerated OHC death was unexpectedly observed relative to that documented in prestin knockout (KO) mice. These observations imply an additional role of prestin in OHC maintenance besides its known requirement for mammalian cochlear amplification. In order to gain mechanistic insights into prestin-associated OHC loss, we implemented several interventions to improve survival. First, 499 prestin KI's were backcrossed to Bak KO mice, which lack the mitochondrial pro-apoptotic gene Bak. Because oxidative stress is implicated in OHC death, another group of 499 prestin KI mice was fed the antioxidant diet, Protandim. 499 KI mice were also backcrossed onto the FVB murine strain, which retains excellent high-frequency hearing well into adulthood, to reduce the compounding effect of age-related hearing loss associated with the original 499 prestin KIs. Finally, a compound heterozygous (chet) mouse expressing one copy of 499 prestin and one copy of KO prestin was also created to reduce quantities of 499 prestin protein. Results show reduction in OHC death in chets, and in 499 prestin KIs on the FVB background, but only a slight improvement in OHC survival for mice receiving Protandim. We also report that improved OHC survival in 499 prestin KIs had little effect on hearing phenotype, reaffirming the original contention about the essential role of prestin's motor function in cochlear amplification. |
| first_indexed | 2024-12-16T07:17:29Z |
| format | Article |
| id | doaj.art-9035fccee7dc49918e659f46f6a316ef |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-16T07:17:29Z |
| publishDate | 2015-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-9035fccee7dc49918e659f46f6a316ef2022-12-21T22:39:44ZengPublic Library of Science (PLoS)PLoS ONE1932-62032015-01-011012e014542810.1371/journal.pone.0145428Prestin-Dependence of Outer Hair Cell Survival and Partial Rescue of Outer Hair Cell Loss in PrestinV499G/Y501H Knockin Mice.Mary Ann CheathamRoxanne M EdgeKazuaki HommaEmily L LesermanPeter DallosJing ZhengA knockin (KI) mouse expressing mutated prestinV499G/Y501H (499 prestin) was created to study cochlear amplification. Recordings from isolated outer hair cells (OHC) in this mutant showed vastly reduced electromotility and, as a consequence, reduced hearing sensitivity. Although 499 prestin OHCs were normal in stiffness and longer than OHCs lacking prestin, accelerated OHC death was unexpectedly observed relative to that documented in prestin knockout (KO) mice. These observations imply an additional role of prestin in OHC maintenance besides its known requirement for mammalian cochlear amplification. In order to gain mechanistic insights into prestin-associated OHC loss, we implemented several interventions to improve survival. First, 499 prestin KI's were backcrossed to Bak KO mice, which lack the mitochondrial pro-apoptotic gene Bak. Because oxidative stress is implicated in OHC death, another group of 499 prestin KI mice was fed the antioxidant diet, Protandim. 499 KI mice were also backcrossed onto the FVB murine strain, which retains excellent high-frequency hearing well into adulthood, to reduce the compounding effect of age-related hearing loss associated with the original 499 prestin KIs. Finally, a compound heterozygous (chet) mouse expressing one copy of 499 prestin and one copy of KO prestin was also created to reduce quantities of 499 prestin protein. Results show reduction in OHC death in chets, and in 499 prestin KIs on the FVB background, but only a slight improvement in OHC survival for mice receiving Protandim. We also report that improved OHC survival in 499 prestin KIs had little effect on hearing phenotype, reaffirming the original contention about the essential role of prestin's motor function in cochlear amplification.http://europepmc.org/articles/PMC4684303?pdf=render |
| spellingShingle | Mary Ann Cheatham Roxanne M Edge Kazuaki Homma Emily L Leserman Peter Dallos Jing Zheng Prestin-Dependence of Outer Hair Cell Survival and Partial Rescue of Outer Hair Cell Loss in PrestinV499G/Y501H Knockin Mice. PLoS ONE |
| title | Prestin-Dependence of Outer Hair Cell Survival and Partial Rescue of Outer Hair Cell Loss in PrestinV499G/Y501H Knockin Mice. |
| title_full | Prestin-Dependence of Outer Hair Cell Survival and Partial Rescue of Outer Hair Cell Loss in PrestinV499G/Y501H Knockin Mice. |
| title_fullStr | Prestin-Dependence of Outer Hair Cell Survival and Partial Rescue of Outer Hair Cell Loss in PrestinV499G/Y501H Knockin Mice. |
| title_full_unstemmed | Prestin-Dependence of Outer Hair Cell Survival and Partial Rescue of Outer Hair Cell Loss in PrestinV499G/Y501H Knockin Mice. |
| title_short | Prestin-Dependence of Outer Hair Cell Survival and Partial Rescue of Outer Hair Cell Loss in PrestinV499G/Y501H Knockin Mice. |
| title_sort | prestin dependence of outer hair cell survival and partial rescue of outer hair cell loss in prestinv499g y501h knockin mice |
| url | http://europepmc.org/articles/PMC4684303?pdf=render |
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