title: The serine-threonine protein kinase PAK4 is dispensable in zebrafish: identification of a morpholino-generated pseudophenotype.
abstract: TALEN-based inactivation of the zebrafish pak4 gene resulted in embryos and adult fish that appear normal and fertile. This is in contrast to our previously published studies which were based on the use of antisense morpholino oligonucleotides (MOs). We have excluded potential explanations such as gene duplication, alternate splicing, cryptic initiation of translation, and translation-independent RNA function. Our conclusion is that pak4 is dispensable in zebrafish, and that even when corroborated by robust controls, such as RNA rescue, MOs may elicit misleading pseudophenotypes that do not correspond to results obtained by genetic mutations, and should thus be used with caution.
authors.affiliation: Section on Vertebrate Development, Program on Genomics of Differentiation, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland, United States of America.
authors.forename: Sheran H W
authors.initials: SH
authors.lastname: Law
authors.affiliation: Section on Vertebrate Development, Program on Genomics of Differentiation, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland, United States of America.
authors.forename: Thomas D
authors.initials: TD
authors.lastname: Sargent
mesh_terms: D000483:Alleles; D000818:Animals; D001483:Base Sequence; D004720:Endonucleases / Q000378:metabolism; D005260:Female; D055786:Gene Knockout Techniques; D054643:INDEL Mutation / Q000235:genetics; D008297:Male; D008969:Molecular Sequence Data; D060172:Morpholinos / Q000494:pharmacology*; D009154:Mutation / Q000235:genetics; D010641:Phenotype; D012313:RNA / Q000235:genetics / Q000378:metabolism; D013312:Stress, Physiological / Q000187:drug effects / Q000235:genetics; D015534:Trans-Activators / Q000378:metabolism; D015027:Zebrafish / Q000196:embryology / Q000378:metabolism*; D029961:Zebrafish Proteins / Q000235:genetics / Q000378:metabolism*; D054462:p21-Activated Kinases / Q000235:genetics / Q000378:metabolism*
chemical_list: D060172:Morpholinos; D015534:Trans-Activators; D029961:Zebrafish Proteins; D012313:RNA; C582412:PAK4 protein, zebrafish; D054462:p21-Activated Kinases; D004720:Endonucleases