Cre-Dependent Optogenetic Transgenic Mice Without Early Age-Related Hearing Loss
Cre-Dependent Optogenetic Transgenic Mice Without Early Age-Related Hearing Loss
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DOI：
10.1101/416164
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发表时间：
2018-09
影响因子：
4.8
通讯作者：
D. Lyngholm;S. Sakata
中科院分区：
文献类型：
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作者：
D. Lyngholm;S. Sakata
随着最近的小鼠遗传技术的出现，现在可以以前所未有的方式研究大脑功能的电路机制。虽然转基因小鼠通常用于C57 BL/6 J（C57）背景，但听力研究通常依赖于不同的遗传背景，例如CBA/Ca或CBA，因为C57小鼠的遗传缺陷导致早期年龄相关的听力损失。这限制了听力研究中可用遗传资源的利用。在这里，我们报告了CBA/Ca背景下的同源（>F10）Cre依赖性通道视紫红质2（ChR 2）小鼠。通过将该品系与C57背景下的Cre-driver小鼠杂交，F1杂交小鼠恢复了C57小鼠的听力缺陷。我们还发现了衰老和听力损失之间的线性关系，其进展率因遗传背景而异（C57为3.39 dB/月; F1杂种为0.82 dB/月）。我们进一步证明，这种方法允许表达ChR 2在一个特定类型的抑制性神经元在听觉皮层，他们可以在清醒小鼠的神经元的同时记录的人口内确定。因此，我们的CBA/Ca背景下的Cre依赖性光遗传学转基因小鼠是研究整个生命周期中听觉回路机制的有价值的工具。
With the advent of recent genetic technologies for mice, it is now feasible to investigate the circuit mechanisms of brain functions in an unprecedented manner. Although transgenic mice are commonly used on C57BL/6J (C57) background, hearing research has typically relied on different genetic backgrounds, such as CBA/Ca or CBA due to the genetic defect of C57 mice for early age-related hearing loss. This limits the utilization of available genetic resources for hearing research. Here we report congenic (>F10) Cre-dependent channelrhodopsin2 (ChR2) mice on CBA/Ca background. By crossing this line with Cre-driver mice on C57 background, F1 hybrids restored the hearing deficit of C57 mice. We also found a linear relationship between aging and hearing loss, with progression rates varied depending on genetic backgrounds (3.39 dB/month for C57; 0.82 dB/month for F1 hybrid). We further demonstrate that this approach allows to express ChR2 in a specific type of inhibitory neurons in the auditory cortex and that they can be identified within a simultaneously recorded population of neurons in awake mice. Thus, our Cre-dependent optogenetic transgenic mice on CBA/Ca background are a valuable tool to investigate the circuit mechanisms of hearing across lifespan.