Pjvk-flox Mouse

Pjvk, also known as DFNB59 and encoding Pejvakin, is a gene within the gasdermin family [3,4,7]. Pejvakin is expressed in sensory hair cells and first-order neurons of the inner ear and is involved in generating auditory and neural signals in the inner ear [2,6]. Mutations in Pjvk cause autosomal recessive non-syndromic hearing impairment (AR-NSHI) of the DFNB59 type, and some cases may also show auditory neuropathy spectrum disorder (ANSD) [1].

In Pjvk -mutant mice, delivery of the PJVK transgene using the synthetic Anc80L65 vector led to robust exogenous pejvakin expression in hair cells and neurons of the cochlea and vestibular organs. This resulted in significant restoration of spiral ganglion neuron density and hair cells in the cochlea, partial recovery of sensorineural hearing impairment, and recovery of vestibular ganglion neurons and balance function to wild-type levels [2]. A knockin mouse model carrying the c.874G > A (p.G292R) variant was generated to study the auditory and vestibular phenotypes of DFNB59, as previous mouse models with different Pjvk defects showed phenotypic variability and inconsistency [5].

In conclusion, Pjvk plays a crucial role in inner-ear function, especially in auditory and vestibular systems. The study of Pjvk -mutant mouse models provides insights into the gene's function in these systems and offers potential for gene-therapy-based solutions for PJVK-related inner-ear deficits, specifically in treating hearing and balance disorders associated with Pjvk mutations [2,5].