Abstract：
Otof, which encodes otoferlin, knockout mice are considered model mice for auditory neuropathy spectrum disorder, which is characterized by an absent auditory brainstem response (ABR) despite preserved distortion product otoacoustic emission (DPOAE). Although otoferlin-deficient mice lack neurotransmitter release at the inner hair cell (IHC) synapse, it remains unclear how the Otof mutation affects spiral ganglions. Thus, we used Otof-mutant mice carrying the Otoftm1a(KOMP)Wtsi allele (Otoftm1a) and analyzed spiral ganglion neurons (SGNs) in Otoftm1a/tm1a mice by immunolabeling type Ⅰ SGNs (SGN-Ⅰ) and type II SGNs (SGN-II). We also examined apoptotic cells in SGNs. Four-week-old Otoftm1a/tm1a mice had an absent ABR but normal DPOAEs. The number of SGNs was significantly lower in Otoftm1a/tm1a mice on postnatal day 7 (P7), P14, and P28 compared with that of wild-type mice. Moreover, significantly more apoptotic SGNs were observed in Otoftm1a/tm1a mice than in wild-type mice on P7, P14, and P28. SGN-IIs were not significantly reduced in Otoftm1a/tm1a mice on P7, P14, and P28. No apoptotic SGN-IIs were observed under our experimental conditions. In summary, Otoftm1a/tm1a mice showed a reduction in SGNs accompanied by apoptosis of SGN-Ⅰs even before the onset of hearing. We speculate that the reduction in SGNs with apoptosis is a secondary defect caused by a lack of otoferlin in IHCs. Appropriate glutamatergic synaptic inputs may be important for the survival of SGNs.
摘要：
奥托夫,编码otoferlin，基因敲除小鼠被认为是听觉神经病变谱系障碍的模型小鼠，尽管保留了失真产物耳声发射（DPOAE），但其特征是听觉脑干反应（ABR）缺失。尽管耳铁蛋白缺陷小鼠缺乏内毛细胞（IHC）突触的神经递质释放，目前尚不清楚Otof突变如何影响螺旋神经节.因此，我们使用携带Otoftm1a（KOMP）Wtsi等位基因（Otoftm1a）的Otof突变小鼠，并通过免疫标记Ⅰ型SGN（SGN-Ⅰ）和Ⅱ型SGN（SGN-Ⅱ）分析了Otoftm1a/tm1a小鼠的螺旋神经节神经元（SGN）。我们还检查了SGN中的凋亡细胞。四周大的Otoftm1a/tm1a小鼠ABR缺失，但DPOAE正常。出生后第7天（P7），Otoftm1a/tm1a小鼠的SGN数量显着降低，与野生型小鼠相比,P14和P28。此外，在P7，P14和P28上，在Otoftm1a/tm1a小鼠中观察到的凋亡SGN明显多于野生型小鼠。在P7，P14和P28上，Otoftm1a/tm1a小鼠的SGN-IIs没有显着降低。在我们的实验条件下没有观察到凋亡SGN-IIs。总之,甚至在听力开始之前，Otoftm1a/tm1a小鼠的SGN减少伴随SGN-Ⅰ的凋亡。我们推测，伴随凋亡的SGN的减少是由IHC中缺乏otoferlin引起的继发性缺陷。适当的谷氨酸能突触输入对于SGN的存活可能是重要的。
