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

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.