Pls1-flox Mouse

Pls1, encoding Plastin 1 (also called fimbrin), is an important member of the fimbrin protein family. It functions as an actin-bundling protein in stereocilia, playing a crucial role in auditory reception by providing structural conformity for the perception of auditory stimuli. In fungi, Pls1 tetraspanins are key factors in the penetration of host plants, likely by re-establishing cell polarity in the appressorium [2,7]. In yeast, Pls1 (formerly Ynl097c-b) is a peroxisomal matrix protein regulating lysine biosynthesis [3].

Mutations in PLS1 have been found to cause autosomal-dominant hereditary hearing loss. For instance, the PLS1 c.981 + 1G>A variant in a Chinese family induced exon 8 skipping, leading to hearing loss. Zebrafish with this variant showed abnormal inner ear phenotypes, and silencing PLS1 expression upregulated genes in the PI3K-Akt signaling pathway [1]. In European and Turkish families, different PLS1 mutations (c.805G>A, p.[E269K]; c.713G>T, p.[L238R]; c.383T>C, p.[F128S]) were identified in autosomal-dominant nonsyndromic hearing loss patients. In silico modeling suggested these variants destabilize the actin-binding domain 1, reducing the protein's ability to bind F-actin, and Pls1-/-mice also showed a similar hearing loss phenotype [4,6]. In Botrytis cinerea, knockdown of BcPls1 by exogenous application of dsRNA led to growth retardation, suggesting its role as a virulence gene [5].

In summary, Pls1 is essential for normal hearing in humans and mice, with its mutations causing hearing loss. In fungi, it is involved in host-plant penetration and virulence. Gene-knockout models, such as Pls1-/-mice, have been crucial in revealing the role of Pls1 in hearing-related biological processes and have implications for understanding the pathogenesis of hearing loss.