Clock genes rescue nphp mutations in zebrafish.

ABSTRACT: The zebrafish pronephros model, using morpholino oligonucleotides (MO) to deplete target genes, has been extensively used to characterize human ciliopathy phenotypes. Recently, discrepancies between MO and genetically defined mutants have questioned this approach. We analyzed zebrafish with mutations in the nphp1-4-8 module to determine the validity of MO-based results. While MO-mediated depletion resulted in glomerular cyst and cloaca malformation, these ciliopathy-typical manifestations were observed at a much lower frequency in zebrafish embryos with defined nphp mutations. All nphp1-4-8 mutant zebrafish were viable and displayed decreased manifestations in the next (F2) generation, lacking maternal RNA contribution. While genetic compensation was further supported by the observation th

SUBMITTER: Kayser N 

PROVIDER: S-EPMC9759334 | biostudies-literature | 2022 Dec

REPOSITORIES: biostudies-literature