Generation and Characterization of α9 and α10 Nicotinic Acetylcholine Receptor Subunit Knockout Mice on a C57BL/6J Background.
Generation and Characterization of α9 and α10 Nicotinic Acetylcholine Receptor Subunit Knockout Mice on a C57BL/6J Background.
复制标题
DOI：
10.3389/fnins.2017.00516
复制
发表时间：
2017
影响因子：
4.3
通讯作者：
Simmons DD
中科院分区：
文献类型：
--
作者：
Morley BJ;Dolan DF;Ohlemiller KK;Simmons DD
我们建立了α9和α10烟碱型乙酰胆碱受体(NAChR)亚单位的结构性基因敲除小鼠模型。然后我们将它们回交到C57BL/6J的遗传背景上。在这篇手稿中，我们报告了菌株的产生和α9和α10结构性敲除以及双重α9α10结构性敲除的听觉表型特征。虽然α9和α10nAChR亚单位与许多生理指标相关，但我们选择用听觉研究来描述小鼠的特征，以将它们与现有的但不同的α9和α10nAChR基因敲除(KO)进行比较。听性脑干反应(ABR)和失真产物耳声发射(DPOAEs)测试显示，所有构成品系的小鼠听力正常。然而，有对侧噪声的DPOAEs(传出适应测量)显示，与野生型对照相比，α9和α10亚基缺失后传出强度显著降低。受试动物为3-8周龄，传出强度与年龄无关。对单成分和双成分KOS的共聚焦研究表明，所有KOS均有异常的耳蜗毛细胞传出神经支配。形态结果与其他用α9或α10nAChR外显子4结构性缺失获得的结果相似。然而，我们的生理学研究结果不同于以前使用由外显子4区域缺失产生的α9 KO并回交到混合Cba/CAJX 129Sv背景上的听觉研究。
We generated constitutive knockout mouse models for the α9 and α10 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 α9 and α10 knockouts and a double α9α10 constitutive knockout. Although the α9 and α10 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 α9 and α10 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 α9 and α10 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 α9 or α10 nAChR. The results of our physiological studies, however, differ from previous auditory studies using a α9 KO generated by deletion of the exon 4 region and backcrossed onto a mixed CBA/CaJ X 129Sv background.
登录
查看更多内容
影响因子：
5.8
作者：
Indurthi, Dinesh C.;Pera, Elena;Chebib, Mary
通讯作者：
Chebib, Mary
影响因子：
10.7
作者：
Lipovsek, Marcela;Fierro, Angelica;Belen Elgoyhen, Ana
通讯作者：
Belen Elgoyhen, Ana
影响因子：
3.5
作者：
Goutman JD;Elgoyhen AB;Gómez-Casati ME
通讯作者：
Gómez-Casati ME
影响因子：
2.5
作者：
Dickerson IM;Bussey-Gaborski R;Holt JC;Jordan PM;Luebke AE
通讯作者：
Luebke AE
影响因子：
1.4
作者：
FOLSOM, RC;OWSLEY, RM
通讯作者：
OWSLEY, RM