Analysis of a Novel Mouse Mutation of the Deafness Gene Pejvakin

Loss of function of the Pejvakin (Pjvk) gene has been associated with deafness induced by cellular stress. This has been postulated to occur due to defective peroxisome biogenesis. Here, we have characterized a novel mouse mutation lacking exon 3 of the Pjvk coding region. A mouse mutant carrying this mutation showed loss of hair cells associated with profound deafness and reduced outer hair cell function. A cell line carrying a deletion of Pjvk exon 3 revealed upregulation of the peroxisomal enzyme catalase upon oxidative stress. In order to further clarify the localization of Pjvk, we introduced amino- and carboxy-terminal tags in its cDNA which failed to confirm its presence in peroxisomes but is likely to be due to mis-targeting of the protein. Our study thus confirms the requirement of Pjvk for maintenance of hair cells and intact hearing and a specific role in peroxisomes upon exposure to cellular stress.