Smpx-KO Mouse

Smpx, short for small muscle protein, X-linked, encodes a 88-amino-acid cytoskeleton-associated protein. It is highly expressed in cardiac and skeletal muscles, as well as fetal inner ears, and is potentially involved in mechanotransduction [4]. Mutations in Smpx can cause X-linked non-syndromic hearing loss, such as X-linked deafness 4 (DFNX4), highlighting its biological importance in the auditory system [1,3,5]. Genetic models like gene-knockout mice are valuable for studying its functions.

In Smpx null mouse models, male mice showed progressive hearing loss starting from high frequency at the 3rd month, while female mice had milder and later-onset hearing loss, similar to human cases. Cochlear morphological analysis revealed progressive degeneration of hair cell bundles from the shortest row, followed by cellular edema, cell death. Exogenous fluorescent Smpx transfection showed its expression in stereocilia, and noise exposure indicated its role in maintaining hair cell bundles, suggesting its importance in the auditory system [1]. In zebrafish, Smpx-deficient models showed inner ear hair cell defects, including a decrease in kinocilia number and structural alterations of stereocilia and kinocilium, impairing mechanotransduction. There was also a clear muscular phenotype with defective muscle fiber organization and function [2]. Additionally, in zebrafish larvae, Smpx was expressed in neuromast mechanosensory hair cells, and loss-of-function experiments showed its role in proper hair cell differentiation, maintenance, and mechanotransduction in the lateral line organ [6].

In conclusion, Smpx is crucial for inner ear development, hair cell bundle maintenance, and muscle development as demonstrated by model-based research. The Smpx null mouse model provides a valuable tool for exploring the pathology of DFNX4, enhancing our understanding of the gene's function in auditory-related diseases [1].

References:

1. Tu, Hailong, Zhang, Aizhen, Fu, Xiaolong, Wang, Haibo, Gao, Jiangang. 2021. SMPX Deficiency Causes Stereocilia Degeneration and Progressive Hearing Loss in CBA/CaJ Mice. In Frontiers in cell and developmental biology, 9, 750023. doi:10.3389/fcell.2021.750023. https://pubmed.ncbi.nlm.nih.gov/34722533/

2. Ghilardi, Anna, Diana, Alberto, Bacchetta, Renato, Prosperi, Laura, Del Giacco, Luca. 2021. Inner Ear and Muscle Developmental Defects in Smpx-Deficient Zebrafish Embryos. In International journal of molecular sciences, 22, . doi:10.3390/ijms22126497. https://pubmed.ncbi.nlm.nih.gov/34204426/

3. Dykxhoorn, Derek M, Tong, Xiaoying, Gosstola, Nicholas C, Liu, Xue Zhong. 2021. Derivation of iPSC line UMi029-A bearing a hearing-loss associated variant in the SMPX gene. In Stem cell research, 54, 102405. doi:10.1016/j.scr.2021.102405. https://pubmed.ncbi.nlm.nih.gov/34052664/

4. Ghilardi, Anna, Diana, Alberto, Prosperi, Laura, Del Giacco, Luca. 2020. Expression pattern of the small muscle protein, X-linked (smpx) gene during zebrafish embryonic and larval developmental stages. In Gene expression patterns : GEP, 36, 119110. doi:10.1016/j.gep.2020.119110. https://pubmed.ncbi.nlm.nih.gov/32197943/

5. Guo, Yingyuan, Hao, Yanru, Zhang, Dejun, Bai, Jie, Guan, Guofang. . A novel missense mutation in SMPX causes a rare form of X-linked postlingual sensorineural hearing loss in a Chinese family. In Translational pediatrics, 10, 378-387. doi:10.21037/tp-20-435. https://pubmed.ncbi.nlm.nih.gov/33708524/

6. Diana, Alberto, Ghilardi, Anna, Del Giacco, Luca. 2024. Differentiation and functioning of the lateral line organ in zebrafish require Smpx activity. In Scientific reports, 14, 7862. doi:10.1038/s41598-024-58138-z. https://pubmed.ncbi.nlm.nih.gov/38570547/