Abstract
Multiple cilia-associated genes have been shown to affect hair cells in zebrafish (Danio rerio), including the human deafness gene dcdc2, the radial spoke gene rsph9, and multiple intraflagellar transport (IFT) and transition zone genes. Recently a zebrafish alms1 mutant was generated. The ALMS1 gene 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 as Alms1 mutant mice show stereocilia polarity defects and a loss of hair cells. Hair cell loss is also seen in postmortem analysis of Alström patients. The zebrafish alms1 mutant has metabolic defects similar to those seen in Alström syndrome and Alms1 mutant mice. We wished to investigate if it also had hair cell defects. We, however, failed to find any hair cell related phenotypes in alms1 mutant 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.
Highlights
Hearing and balance disorders are common sensory disorders [1, 2]
We found that alms1 mutant zebrafish had normal cilia formation in lateral line hair cells and other ciliated cells similar to what has been observed in mammalian Alms1 mutants
Cilia in Alms1 mutant mice and fibroblasts isolated from Alstrom syndrome patients appear grossly normal [40, 46, 51,52,53] even when there is no visible antibody labeling for ALMS1 protein [52]
Summary
Hearing and balance disorders are common sensory disorders [1, 2]. There is a significant genetic component to these disorders, with over 50% of congenital hearing loss seen in newborns being hereditary [3]. Other cilia genes associated with hearing loss in humans include DCDC2, CDC14A, CCDC114, and the basal body genes CEP78 and CEP250 [23,24,25,26,27,28] While some of these genes, such as dcdc, are necessary for hair cell function in zebrafish [26] others such as cdc14A do not cause zebrafish hair cell phenotypes when mutated [29]. Zebrafish alms mutants share many phenotypes with Alstrom Syndrome patients, including retinal degeneration, kidney and cardiac defects, increased fat disposition in the liver, a propensity for obesity, hyperinsulinemia, and glucose response defects [36]. It shows that cilia-associated genes have distinct roles in different hair cell types
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