alms1 mutant zebrafish do not show hair cell phenotypes seen in other cilia mutants

Abstract

Multiple cilia-associated genes have been shown to affect hair cells in zebrafish (Danio rerio), including the human deafness genedcdc2, the radial spoke genersph9, and multiple intraflagellar transport (IFT) and transition zone genes. Recently a zebrafishalms1mutant was generated. TheALMS1gene is the gene mutated in the ciliopathy Alström Syndrome a disease that causes hearing loss among other symptoms. The hearing loss seen in Alström Syndrome may be due in part to hair cell defects asAlms1mutant mice show stereocilia polarity defects and a loss of hair cells. Hair cell loss is also seen in postmortem analysis of Alström patients. The zebrafishalms1mutant has metabolic defects similar to those seen in Alström syndrome andAlms1mutant mice. We wished to investigate if it also had hair cell defects. We, however, failed to find any hair cell related phenotypes inalms1mutant zebrafish. They had normal lateral line hair cell numbers as both larvae and adults and normal kinocilia formation. They also showed grossly normal swimming behavior, response to vibrational stimuli, and FM1-43 loading. Mutants also showed a normal degree of sensitivity to both short-term neomycin and long-term gentamicin treatment. These results indicate that cilia-associated genes differentially affect different hair cell types.