Loxhd1-KO Mouse

Loxhd1, encoding lipoxygenase homology domain 1, is crucial for the mechanotransduction process in cochlear hair cells [1]. It consists of 15 polycystin lipoxygenase α -toxin (PLAT) repeats which can bind lipids and proteins, and is distributed along the length of stereocilia. Its function is essential for normal hearing as it is involved in the sound detection process in the inner ear [1].

Two Loxhd1 mouse models with mutations in the 10th PLAT repeat exhibited mechanotransduction defects. In these mutants, while mechanotransduction currents in inner hair cells (IHCs) were similar to wild-type levels in the first postnatal week, they were severely affected by postnatal day 11 [1]. Additionally, studies using mouse models showed that LOXHD1 is essential for keeping TMC1-pore forming subunits at the tip link in the hair bundle, but is dispensable for TMC2 [2,3]. LOXHD1 selectively interacts with TMC1, CIB2, LHFPL5, and tip-link protein PCDH15 [2,3].

In conclusion, Loxhd1 is indispensable for the mechanotransduction in cochlear hair cells and maintaining TMC1-driven mature auditory channels at the site of force transmission. Mouse models with Loxhd1 mutations have revealed its critical role in normal hearing function, and its malfunction is associated with non-syndromic sensorineural hearing loss (NSHL) such as DFNB77 [1,2,3,4].