Lypd1-DTR/+: A New Mouse Model for Specifically Damaging the Type Ic Spiral Ganglion Neurons of the Cochlea
Lypd1-DTR/+: A New Mouse Model for Specifically Damaging the Type Ic Spiral Ganglion Neurons of the Cochlea
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DOI：
10.1007/s12264-023-01071-4
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发表时间：
2023-05
影响因子：
5.6
通讯作者：
Di Zhang;Minhui Ren;Zhenghong Bi;Yunpeng Gu;Shuting Li;Guangqin Wang;Xiang Li;Zhiyong Liu
中科院分区：
文献类型：
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作者：
Di Zhang;Minhui Ren;Zhenghong Bi;Yunpeng Gu;Shuting Li;Guangqin Wang;Xiang Li;Zhiyong Liu
已接受：2023年5月7日/在线发布时间：2023年5月24日©中国科学院脑科学与智能技术卓越研究中心2023参与烟碱乙酰胆碱受体活性的调节[8]。值得注意的是，Lypd 1在成年耳蜗中的Ic型SGN中表达水平最高，而在Ib和Ia型SGN中表达水平最低[3-5]。此外，两种内在转录因子Neurod 1和Runx 1促进未分化的SGN前体进入Ic或Ic/Ib分化轨道[6，9]。最后，在I型SGN的多样化中也需要通过IHC和SGN之间的突触的IHC驱动的活动[3，4]。囊泡谷氨酸转运体3型（vGlut 3，由Slc 17 a8编码）是从IHC释放谷氨酸所必需的[10，11]，因此，vGlut 3-/-小鼠显示出显著降低的Ic型SGN百分比和表达高水平Calb 2的Ia型SGN的过度产生[3，4]。Ic型SGN呈现出几个显著特征：首先，它们具有低自发放电率[3];第二，它们在IHC的蜗轴侧形成具有较大突触前带的突触[3-5];第三，它们选择性地易受衰老影响[3]。因此，预期小鼠中Ic型SGN的退化与人类年龄相关性听力损失（ARHL）或老年性耳聋（老年人中最常见的感觉障碍形式）非常相似[12]。然而，具有Ic型SGN特异性损伤的小鼠模型尚未可用。
Accepted: 7 May 2023/Published online: 24 May 2023© Center for Excellence in Brain Science and Intelligence Technology, Chinese Academy of Sciences 2023 involved in modulating the activity of nicotinic acetylcholine receptors [8]. Notably, Lypd1 is expressed at the highest level in type Ic SGNs and minimally expressed in Ib and Ia SGNs in adult cochleae [3–5]. Moreover, two intrinsic transcription factors, Neurod1 and Runx1, promote the entry of undifferentiated SGN precursors into the Ic or Ic/Ib differentiation track [6, 9]. Lastly, IHC-driven activity through synapses between IHCs and SGNs is also required in the diversification of type I SGNs [3, 4]. Vesicular glutamate transporter type 3 (vGlut3, encoded by Slc17a8) is essential for glutamate release from IHCs [10, 11], and, accordingly, vGlut3–/–mice show drastically reduced percentages of type Ic SGNs and overproduction of type Ia SGNs expressing high levels of Calb2 [3, 4].Type Ic SGNs present a few notable features: First, they have a low spontaneous firing rate [3]; second, they form synapses with larger presynaptic ribbons at the modiolar side of IHCs [3–5]; and third, they are selectively vulnerable to aging [3]. Thus, degeneration of type Ic SGNs in mice is expected to closely mimic human age-related hearing loss (ARHL), or presbycusis, the most common form of sensory impairment among older adults [12]. However, a mouse model with specific damage of type Ic SGNs is not yet available.