| First Author | Morley BJ | Year | 2017 |
| Journal | Front Neurosci | Volume | 11 |
| Pages | 516 | PubMed ID | 28983232 |
| Mgi Jnum | J:268887 | Mgi Id | MGI:6272535 |
| Doi | 10.3389/fnins.2017.00516 | Citation | Morley BJ, et al. (2017) Generation and Characterization of alpha9 and alpha10 Nicotinic Acetylcholine Receptor Subunit Knockout Mice on a C57BL/6J Background. Front Neurosci 11:516 |
| abstractText | We generated constitutive knockout mouse models for the alpha9 and alpha10 nicotinic acetylcholine receptor (nAChR) subunits by derivation from conditional knockouts by breeding with CRE deleter mice. We then backcrossed them onto a C57BL/6J genetic background. In this manuscript, we report the generation of the strains and an auditory phenotypic characterization of the constitutive alpha9 and alpha10 knockouts and a double alpha9alpha10 constitutive knockout. Although the alpha9 and alpha10 nAChR subunits are relevant to a number of physiological measures, we chose to characterize the mouse with auditory studies to compare them to existing but different alpha9 and alpha10 nAChR knockouts (KOs). Auditory brainstem response (ABR) measurements and distortion product otoacoustic emissions (DPOAEs) showed that all constitutive mouse strains had normal hearing. DPOAEs with contralateral noise (efferent adaptation measurements), however, showed that efferent strength was significantly reduced after deletion of both the alpha9 and alpha10 subunits, in comparison to wildtype controls. Animals tested were 3-8 weeks of age and efferent strength was not correlated with age. Confocal studies of single and double constitutive KOs showed that all KOs had abnormal efferent innervation of cochlear hair cells. The morphological results are similar to those obtained in other strains using constitutive deletion of exon 4 of alpha9 or alpha10 nAChR. The results of our physiological studies, however, differ from previous auditory studies using a alpha9 KO generated by deletion of the exon 4 region and backcrossed onto a mixed CBA/CaJ X 129Sv background. |
