# The P4-phospholipid flippase Atp11a is required for maintenance of eye and ear structure in zebrafish

## TL;DR

This study shows that the atp11a gene is essential for maintaining eye and ear structures in zebrafish, and its mutation leads to hearing loss and photoreceptor degradation.

## Contribution

The study introduces a zebrafish model for atp11a-related hearing loss and reveals its role in photoreceptor maintenance.

## Key findings

- Atp11a mutant zebrafish have fewer stereocilia in the ear and hair cells in neuromasts.
- Mutant zebrafish raised in the dark show less severe photoreceptor degradation.
- Photoreceptor defects in mutants are linked to mitochondrial fission and energy homeostasis issues.

## Abstract

The atp11a gene encodes a phospholipid flippase protein required to flip phosphatidylserine (PS) and phosphatidylethanolamine (PE) from the outer leaflet of the cytoplasmic membrane to the inner leaflet. Mutations in ATP11A have been described in individuals with sensorineural hearing loss and neurological deterioration; however, little is known regarding the mechanism by which loss of atp11a results in such phenotypes. To this end, we created loss-of-function atp11a mutant zebrafish to characterize potential disease states. We demonstrate that mutant atp11a zebrafish display a reduced number of stereocilia in the larval ear and a reduced number of hair cells in some sensory neuromasts, indicating that these fish represent an ideal model for studying atp11a-attributable hearing loss. In addition, atp11a mutant zebrafish raised in a standard light cycle have reduced photoreceptor outer segments, the severity of which is lessened when mutant larvae are raised in the dark. Photoreceptors that do remain in homozygous atp11a mutants undergo mitochondrial fission and produce an increased number of mitochondria, suggesting that defects in energy homeostasis may contribute to or result from outer segment degradation.

Highlighted Article:
Mutation of atp11a in zebrafish causes photoreceptor degradation and defects in the ear and lateral line neuromast system.