Abstract
A chimera is a genetic composite containing a unique mix of cells derived from more than one zygote. This mouse model allows one to learn how cells of contrasting genotype functionally interact in vivo. Here, we investigate the effect that different proportions of prestin-containing outer hair cells (OHC) have on cochlear amplification. To address this issue, we developed a prestin chimeric mouse in which both ROSA26 wild-type (WT) and prestin knock-out (KO) genotypes are present in a single cochlea. The WT ROSA26 mice express a cell marker, allowing one to identify cells originating from the WT genome. Examination of cochlear tissue indicated that prestin chimeric mice demonstrate a mosaic in which mutant and normal OHCs interleave along the cochlear partition, similar to all other chimeric mouse models. The anatomical distribution of prestin-containing OHCs was compared with physiological data including thresholds and tuning curves for the compound action potential (CAP) recorded in anesthetized mice. Analysis of these measures did not reveal mixed phenotypes in which the distribution of prestin-containing OHCs impacted sensitivity and frequency selectivity to different degrees. However, by reducing the number of prestin-containing OHCs, phenotypes intermediate between WT and KO response patterns were obtained. Accordingly, we demonstrate a proportional reduction in sensitivity and in the tip length of CAP tuning curves as the number of OHCs derived from the KO genome increases; i.e., genotype ratio and phenotype are closely related.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 12000-12008 |
| Number of pages | 9 |
| Journal | Journal of Neuroscience |
| Volume | 29 |
| Issue number | 38 |
| DOIs | |
| State | Published - Sep 23 2009 |
Fingerprint
ASJC Scopus subject areas
- Neuroscience(all)
Cite this
}
A chimera analysis of prestin knock-out mice. / Cheatham, Mary Ann; Low-Zeddies, Sharon; Naik, Khurram; Edge, Roxanne; Zheng, Jing; Anderson, Charles T.; Dallos, Peter.
In: Journal of Neuroscience, Vol. 29, No. 38, 23.09.2009, p. 12000-12008.Research output: Contribution to journal › Article
TY - JOUR
T1 - A chimera analysis of prestin knock-out mice
AU - Cheatham, Mary Ann
AU - Low-Zeddies, Sharon
AU - Naik, Khurram
AU - Edge, Roxanne
AU - Zheng, Jing
AU - Anderson, Charles T.
AU - Dallos, Peter
PY - 2009/9/23
Y1 - 2009/9/23
N2 - A chimera is a genetic composite containing a unique mix of cells derived from more than one zygote. This mouse model allows one to learn how cells of contrasting genotype functionally interact in vivo. Here, we investigate the effect that different proportions of prestin-containing outer hair cells (OHC) have on cochlear amplification. To address this issue, we developed a prestin chimeric mouse in which both ROSA26 wild-type (WT) and prestin knock-out (KO) genotypes are present in a single cochlea. The WT ROSA26 mice express a cell marker, allowing one to identify cells originating from the WT genome. Examination of cochlear tissue indicated that prestin chimeric mice demonstrate a mosaic in which mutant and normal OHCs interleave along the cochlear partition, similar to all other chimeric mouse models. The anatomical distribution of prestin-containing OHCs was compared with physiological data including thresholds and tuning curves for the compound action potential (CAP) recorded in anesthetized mice. Analysis of these measures did not reveal mixed phenotypes in which the distribution of prestin-containing OHCs impacted sensitivity and frequency selectivity to different degrees. However, by reducing the number of prestin-containing OHCs, phenotypes intermediate between WT and KO response patterns were obtained. Accordingly, we demonstrate a proportional reduction in sensitivity and in the tip length of CAP tuning curves as the number of OHCs derived from the KO genome increases; i.e., genotype ratio and phenotype are closely related.
AB - A chimera is a genetic composite containing a unique mix of cells derived from more than one zygote. This mouse model allows one to learn how cells of contrasting genotype functionally interact in vivo. Here, we investigate the effect that different proportions of prestin-containing outer hair cells (OHC) have on cochlear amplification. To address this issue, we developed a prestin chimeric mouse in which both ROSA26 wild-type (WT) and prestin knock-out (KO) genotypes are present in a single cochlea. The WT ROSA26 mice express a cell marker, allowing one to identify cells originating from the WT genome. Examination of cochlear tissue indicated that prestin chimeric mice demonstrate a mosaic in which mutant and normal OHCs interleave along the cochlear partition, similar to all other chimeric mouse models. The anatomical distribution of prestin-containing OHCs was compared with physiological data including thresholds and tuning curves for the compound action potential (CAP) recorded in anesthetized mice. Analysis of these measures did not reveal mixed phenotypes in which the distribution of prestin-containing OHCs impacted sensitivity and frequency selectivity to different degrees. However, by reducing the number of prestin-containing OHCs, phenotypes intermediate between WT and KO response patterns were obtained. Accordingly, we demonstrate a proportional reduction in sensitivity and in the tip length of CAP tuning curves as the number of OHCs derived from the KO genome increases; i.e., genotype ratio and phenotype are closely related.
UR - http://www.scopus.com/inward/record.url?scp=70349307306&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=70349307306&partnerID=8YFLogxK
U2 - 10.1523/JNEUROSCI.1651-09.2009
DO - 10.1523/JNEUROSCI.1651-09.2009
M3 - Article
VL - 29
SP - 12000
EP - 12008
JO - Journal of Neuroscience
JF - Journal of Neuroscience
SN - 0270-6474
IS - 38
ER -