Li Siyu, Qiu Yue, Li Ao, Lu Jie, Ji Xinya, Hao Wenli, Cheng Cheng, Gao Xia
Department of Otolaryngology Head and Neck Surgery, Jiangsu Provincial Key Medical Discipline (Laboratory), Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing, China.
Northern Jiangsu People's Hospital Affiliated to Yangzhou University, Yangzhou, China.
Otol Neurotol. 2025 Apr 1;46(4):e139-e146. doi: 10.1097/MAO.0000000000004449. Epub 2025 Feb 14.
In this study, we aimed to examine the cochlear expression pattern and function of Striatin-interacting protein 2 (STRIP2) by using animal models.
Sensorineural hearing loss often results from genetic defects in hair cell (HC) development and function. STRIP2 is a part of the striatin-interacting phosphatase and kinase (STRIPAK) complex, which plays important regulatory roles in cell fate determination, proliferation, cytoskeletal organization, and cell morphology. A recent study revealed Strip2 as the candidate gene that regulates positive selection in HC lineages. However, its role in the inner ear has not been identified.
Strip2 knockout mouse model was used to examine the cochlear expression pattern and function of STRIP2. Auditory brainstem response test was used to evaluate the hearing function of mice. Immunostaining and scanning electron microscope were used to study hair cells, synapses, and stereocilia of cochlea.
Immunostaining showed that cytoplasmic STRIP2 expression in hair cells increased from postnatal day (P) 3 to P14. Despite having normal hearing thresholds, hair cell numbers, and stereocilia morphology until P90, the deletion of Strip2 resulted in a mild reduction in ribbon synapse density, suggesting a late onset of cochlear synaptic defects.
Our results revealed that STRIP2 was abundantly expressed in hair cells; however, the hearing function of Strip2-/- mice was comparable to that of control mice until P90, and a mild decrease in ribbon synapse number was detected at P60 and P90. Further studies on STRIP2 and its associated complexes will provide new insights into the pathways involved in inner ear development and function.
在本研究中，我们旨在通过动物模型研究条纹蛋白相互作用蛋白2（STRIP2）的耳蜗表达模式和功能。
感音神经性听力损失通常源于毛细胞（HC）发育和功能的基因缺陷。STRIP2是条纹蛋白相互作用磷酸酶和激酶（STRIPAK）复合物的一部分，该复合物在细胞命运决定、增殖、细胞骨架组织和细胞形态中发挥重要调节作用。最近的一项研究表明Strip2是调节HC谱系中阳性选择的候选基因。然而，其在内耳中的作用尚未明确。
使用Strip2基因敲除小鼠模型研究STRIP2的耳蜗表达模式和功能。采用听觉脑干反应测试评估小鼠的听力功能。利用免疫染色和扫描电子显微镜研究耳蜗的毛细胞、突触和静纤毛。
免疫染色显示，毛细胞中细胞质STRIP2的表达从出生后第3天（P3）到P14增加。尽管直到P90时听力阈值、毛细胞数量和静纤毛形态均正常，但Strip2的缺失导致带状突触密度轻度降低，提示耳蜗突触缺陷出现较晚。
我们结果显示，STRIP2在毛细胞中大量表达；然而，直到P90时，Strip2基因敲除小鼠的听力功能与对照小鼠相当，且在P60和P9时检测到带状突触数量轻度减少。对STRIP2及其相关复合物的进一步研究将为内耳发育和功能相关途径提供新的见解。
