Fscn2, also known as Fascin2, encodes an actin cross-linking protein. It is involved in the formation of hair cell stereocilia and retina structure, and may play a role in cell migration and invasion as part of the FSCN family [2,5]. Mutations in Fscn2 have been linked to hearing impairment and retinal degeneration in humans and mice, suggesting its importance in maintaining ear and eye function [2,4]. Genetic mouse models are valuable for studying Fscn2 function.

In Fscn2 knockout mice, there is progressive loss of hearing and hair cells, along with upregulation of PARVB, which leads to inhibition of the ILK-AKT pathway and cochlear cell death [2]. These mice also show progressive photoreceptor degeneration, structural abnormalities of the outer segment, and depressed rod and cone electroretinograms, indicating that haploinsufficiency of Fscn2 may result in photoreceptor degeneration, similar to human autosomal dominant retinitis pigmentosa [1]. Additionally, Fscn2-/-mice are more susceptible to cisplatin-induced hearing impairment and cochlear cell apoptosis [3].

In conclusion, Fscn2 is essential for maintaining ear and eye function. Gene knockout mouse models have revealed its role in preventing cochlear cell death and photoreceptor degeneration, providing insights into the mechanisms of genetic hearing loss and retinal diseases. High expression of Fscn2 may also be a favorable biomarker for predicting clinical outcomes in multiple myeloma [2,3,4,5].

References:

1. Yokokura, Shunji, Wada, Yuko, Nakai, Shigeyasu, Tamai, Makoto, Noda, Tetsuo. . Targeted disruption of FSCN2 gene induces retinopathy in mice. In Investigative ophthalmology & visual science, 46, 2905-15. doi:. https://pubmed.ncbi.nlm.nih.gov/16043865/

2. Liu, Rongrong, Shang, Wenjing, Liu, Yingying, Song, Xicheng, Han, Fengchan. 2024. Inhibition of the ILK-AKT pathway by upregulation of PARVB contributes to the cochlear cell death in Fascin2 gene knockout mice. In Cell death discovery, 10, 89. doi:10.1038/s41420-024-01851-5. https://pubmed.ncbi.nlm.nih.gov/38374196/

3. Wang, Yan, Liu, Yingying, Xie, Yi, Shang, Wenjing, Han, Fengchan. 2024. Loss of Fascin2 increases susceptibility to cisplatin-induced hearing impairment and cochlear cell apoptosis in mice. In Journal of otology, 19, 133-139. doi:10.1016/j.joto.2024.07.001. https://pubmed.ncbi.nlm.nih.gov/39735238/

4. Liu, Xiang, Zhao, Mengmeng, Xie, Yi, Jin, Changzhu, Han, Fengchan. 2018. Null Mutation of the Fascin2 Gene by TALEN Leading to Progressive Hearing Loss and Retinal Degeneration in C57BL/6J Mice. In G3 (Bethesda, Md.), 8, 3221-3230. doi:10.1534/g3.118.200405. https://pubmed.ncbi.nlm.nih.gov/30082328/

5. Deng, Cong, Si, Chaozeng, Ye, Xu, Zheng, Yongjiang, Qian, Tingting. 2021. Prognostic significance of FSCN family in multiple myeloma. In Journal of Cancer, 12, 1936-1944. doi:10.7150/jca.53675. https://pubmed.ncbi.nlm.nih.gov/33753991/