Pls1-KO Mouse

Pls1, encoding Plastin 1 (also called fimbrin), is an important member of the fimbrin protein family. In humans, it is highly expressed in stereocilia where it functions as an actin-bundling protein, essential for the regular maintenance of stereocilia and thus auditory reception [4,5]. In yeast, it is a peroxisomal matrix protein that regulates lysine biosynthesis [3]. In plant-pathogenic fungi, Pls1 tetraspanins are key factors for penetration into host plants, likely by re-establishing polarized growth in the appressorium [2,6].

Mutations in PLS1 have been found to cause autosomal-dominant hereditary hearing loss. A novel PLS1 c.981 + 1G>A variant was identified in a Chinese family, which causes hearing loss by inducing exon 8 skipping. In zebrafish, this variant led to abnormal inner-ear phenotypes and changes in swimming ability. Also, silencing PLS1 expression upregulated genes in the PI3K-Akt signaling pathway [1]. In European and Turkish families, different PLS1 mutations were associated with autosomal-dominant nonsyndromic hearing loss, and in silico protein modeling suggested these mutations destabilize the actin-binding domain, reducing the protein's ability to bind F-actin [4,5].

In conclusion, Pls1 plays crucial roles in auditory function, lysine biosynthesis, and fungal plant-host interactions. The identification of PLS1 mutations causing hearing loss in humans and similar phenotypes in animal models like zebrafish and mice contributes to understanding the molecular mechanisms of hearing loss, providing potential targets for future therapeutic strategies in this disease area [1,4,5].