Deletion of Limk1 and Limk2 in mice does not alter cochlear development or auditory function
Deletion of Limk1 and Limk2 in mice does not alter cochlear development or auditory function
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小鼠中 Limk1 和 Limk2 的缺失不会改变耳蜗发育或听觉功能
DOI：
10.1038/s41598-019-39769-z
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发表时间：
2019-03-04
影响因子：
4.6
通讯作者：
Chen, Fangyi
中科院分区：
文献类型：
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作者：
Fang, Qiaojun;Zhang, Yuhua;Chen, Fangyi
遗传性听力损失与导致感觉毛细胞（HC）功能障碍的基因突变有关。HC结构由细胞骨架定义，细胞骨架主要由肌动蛋白丝和肌动蛋白结合伴侣组成。含LIM基序的蛋白激酶（LIMKs）是肌动蛋白动力学的主要调节因子，由LIMK 1和LIMK 2两个成员组成。肌动蛋白排列直接参与中枢神经系统中细胞骨架结构的调节和突触的成熟，并且LIMKs通过控制嗅觉系统和海马中肌动蛋白解聚蛋白cofilin的活化而参与结构可塑性。然而，LIMKs在小鼠耳蜗发育和突触功能中的表达模式和作用还需要进一步研究。我们在这里表明，Limk基因在小鼠耳蜗中表达。我们检查了形态学和传入突触密度的毛细胞，并测量了Limk 1和Limk 2双敲除（DKO）小鼠的听觉功能。我们发现，Limk 1和Limk 2的缺失似乎不会影响耳蜗的整体发育，包括毛细胞的数量和毛束的结构。DKO小鼠和野生型同窝小鼠之间的听觉阈值没有显著差异。然而，在DKO小鼠中p-切丝蛋白的表达显著降低。此外，在DKO和野生型小鼠之间的带状突触的数量或分布中没有发现显著差异。总之，我们的数据表明，Limk基因在耳蜗发育中发挥的作用与它们在中枢神经系统中的作用不同。
Inherited hearing loss is associated with gene mutations that result in sensory hair cell (HC) malfunction. HC structure is defined by the cytoskeleton, which is mainly composed of actin filaments and actin-binding partners. LIM motif-containing protein kinases (LIMKs) are the primary regulators of actin dynamics and consist of two members: LIMK1 and LIMK2. Actin arrangement is directly involved in the regulation of cytoskeletal structure and the maturation of synapses in the central nervous system, and LIMKs are involved in structural plasticity by controlling the activation of the actin depolymerization protein cofilin in the olfactory system and in the hippocampus. However, the expression pattern and the role of LIMKs in mouse cochlear development and synapse function also need to be further studied. We show here that the Limk genes are expressed in the mouse cochlea. We examined the morphology and the afferent synapse densities of HCs and measured the auditory function in Limk1 and Limk2 double knockout (DKO) mice. We found that the loss of Limk1 and Limk2 did not appear to affect the overall development of the cochlea, including the number of HCs and the structure of hair bundles. There were no significant differences in auditory thresholds between DKO mice and wild-type littermates. However, the expression of p-cofilin in the DKO mice was significantly decreased. Additionally, no significant differences were found in the number or distribution of ribbon synapses between the DKO and wild-type mice. In summary, our data suggest that the Limk genes play a different role in the development of the cochlea compared to their role in the central nervous system.