Smpx-KO Mouse

Smpx, or small muscle protein, X-linked, encodes an 88-amino-acid protein. It is involved in important biological processes, with its malfunction causing X-linked non-syndromic hearing loss (DFNX4) [1,2,3,4,6]. It may also play a role in muscle development as it has been found to interact with MUSTN1 which regulates muscle development and regeneration [5].

In gene-knockout studies, male Smpx null mice generated by CRISPR-Cas9 showed progressive hearing loss starting from high frequency at 3 months, while female mice had milder and later-onset hearing loss, similar to human cases. Morphological analysis of mouse cochleas revealed progressive degeneration of hair cell bundles from the shortest row, followed by cellular edema and cell death. Transfection experiments showed Smpx expression in stereocilia, and noise exposure indicated its role in maintaining hair cell bundles [1]. In zebrafish, Smpx-deficient models demonstrated inner ear and muscle developmental defects, including a decrease in kinocilia number, structural alterations of stereocilia and kinocilium in inner-ear hair cells, and impairment of hair-cell mechanotransduction [2].

In conclusion, Smpx is crucial for the normal development and function of the inner ear and may also contribute to muscle development. The Smpx-knockout mouse and zebrafish models have provided valuable insights into the pathology of DFNX4 and the role of Smpx in inner-ear and muscle development, facilitating a better understanding of the associated biological processes and disease mechanisms [1,2].

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. Arifuzzaman, Md, Mitra, Sarmistha, Das, Raju, Absar, Nurul, Dash, Raju. 2019. In silico analysis of nonsynonymous single-nucleotide polymorphisms (nsSNPs) of the SMPX gene. In Annals of human genetics, 84, 54-71. doi:10.1111/ahg.12350. https://pubmed.ncbi.nlm.nih.gov/31583691/

4. 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/

5. Fu, Yu, Hao, Xin, Shang, Peng, Zhang, Bo, Zhang, Hao. 2025. MUSTN1 Interaction With SMPX Regulates Muscle Development and Regeneration. In Cell proliferation, , e13809. doi:10.1111/cpr.13809. https://pubmed.ncbi.nlm.nih.gov/39828423/

6. 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/