Myh14-KO Mouse

Myh14, a member of the myosin family, is involved in many motile processes such as ion-channel gating, organelle translocation, and cytoskeleton rearrangement [5]. Although its exact associated pathways are not comprehensively detailed in the provided references, its importance lies in its implications for auditory function and potential roles in cancer-related processes. Genetic models, like mouse models, can be valuable in studying Myh14's functions.

In terms of auditory function, Myh14 knockout (Myh14-/-) mice in CBA/CaJ background did not show significant hearing loss until five months of age. However, they were more vulnerable to high-intensity noise compared to control mice, with more significant outer hair cell loss after acoustic trauma, suggesting Myh14 may protect the cochlea after acoustic overstimulation [5].

In endometrial cancer, bioinformatics and functional studies showed that Myh14 was an independent and unfavorable prognostic indicator. It impaired cell sensitivity to chemotherapy drugs and progesterone, increased cell proliferation and metastasis, and activated the Wnt/β-catenin signaling pathway. Sesamolin, a natural compound, targeted Myh14 and attenuated endometrial cancer progression [2].

Additionally, Myh14 mutations have been associated with autosomal-dominant sensorineural hearing loss. In a study of six unrelated families, five Myh14 variants were identified, two of which were classified as likely pathogenic, and in-silico modeling indicated they could alter protein stability and interactions [1]. A novel missense variant in Myh14 was also identified as the pathogenic cause of postlingual nonsyndromic autosomal-dominant sensorineural hearing loss in a Chinese family [3]. A German patient with a loss-of-function variant in Myh14 presented with a severe and rapidly progressive neuromuscular disorder phenotype including distal myopathy, early respiratory failure, dysphagia, hoarseness, and peripheral neuropathy, expanding the clinical spectrum of Myh14-related neuromuscular disorders [4].

In conclusion, Myh14 plays important roles in auditory function, potentially protecting the cochlea from acoustic overstimulation. Its mutations are associated with autosomal-dominant sensorineural hearing loss. In endometrial cancer, it promotes cancer progression through the Wnt/β-catenin signaling pathway. The study of Myh14 knockout mouse models has been crucial in revealing its role in auditory function, and its implications in disease provide potential targets for treatment in hearing-loss-related and cancer-related conditions.

References:

1. Duman, Duygu, Ramzan, Memoona, Subasioglu, Asli, Bademci, Guney, Tekin, Mustafa. 2024. Identification of novel MYH14 variants in families with autosomal dominant sensorineural hearing loss. In American journal of medical genetics. Part A, 194, e63563. doi:10.1002/ajmg.a.63563. https://pubmed.ncbi.nlm.nih.gov/38352997/

2. Lin, Yibin, Chen, Xiao, Lin, Linping, Zhu, Xiaofeng, Lin, Xian. 2024. Sesamolin serves as an MYH14 inhibitor to sensitize endometrial cancer to chemotherapy and endocrine therapy via suppressing MYH9/GSK3β/β-catenin signaling. In Cellular & molecular biology letters, 29, 63. doi:10.1186/s11658-024-00583-9. https://pubmed.ncbi.nlm.nih.gov/38698330/

3. Wang, Mingming, Zhou, Yicui, Zhang, Fengguo, Bai, Xiaohui, Wang, Haibo. 2020. A novel MYH14 mutation in a Chinese family with autosomal dominant nonsyndromic hearing loss. In BMC medical genetics, 21, 154. doi:10.1186/s12881-020-01086-y. https://pubmed.ncbi.nlm.nih.gov/32711451/

4. Mensch, Alexander, Jordan, Berit, Weis, Joachim, Zierz, Stephan, Naegel, Steffen. . A Novel MYH14 Variant Presenting as a New Phenotype of MYH14-Associated Neuromuscular Disorders-Clinicohistologic Findings and Review of the Literature. In Journal of clinical neuromuscular disease, 26, 55-62. doi:10.1097/CND.0000000000000469. https://pubmed.ncbi.nlm.nih.gov/39590923/

5. Fu, Xiaolong, Zhang, Linqing, Jin, Yecheng, Xia, Ming, Gao, Jiangang. 2016. Loss of Myh14 Increases Susceptibility to Noise-Induced Hearing Loss in CBA/CaJ Mice. In Neural plasticity, 2016, 6720420. doi:10.1155/2016/6720420. https://pubmed.ncbi.nlm.nih.gov/28101381/