title: In vivo mutation of pre-mRNA processing factor 8 (Prpf8) affects transcript splicing, cell survival and myeloid differentiation.
abstract: Mutated spliceosome components are recurrently being associated with perturbed tissue development and disease pathogenesis. Cephalophŏnus (cph), is a zebrafish mutant carrying an early premature STOP codon in the spliceosome component Prpf8 (pre-mRNA processing factor 8). Cph initially develops normally, but then develops widespread cell death, especially in neurons, and is embryonic lethal. Cph mutants accumulate aberrantly spliced transcripts retaining both U2- and U12-type introns. Within early haematopoiesis, myeloid differentiation is impaired, suggesting Prpf8 is required for haematopoietic development. Cph provides an animal model for zygotic PRPF8 dysfunction diseases and for evaluating therapeutic interventions.
authors.affiliation: Australian Regenerative Medicine Institute, Monash University, Clayton, Victoria 3800, Australia.
authors.forename: Maria-Cristina
authors.initials: MC
authors.lastname: Keightley
authors.forename: Meredith O
authors.initials: MO
authors.lastname: Crowhurst
authors.forename: Judith E
authors.initials: JE
authors.lastname: Layton
authors.forename: Traude
authors.initials: T
authors.lastname: Beilharz
authors.forename: Sebastian
authors.initials: S
authors.lastname: Markmiller
authors.forename: Sony
authors.initials: S
authors.lastname: Varma
authors.forename: Benjamin M
authors.initials: BM
authors.lastname: Hogan
authors.forename: Tanya A
authors.initials: TA
authors.lastname: de Jong-Curtain
authors.forename: Joan K
authors.initials: JK
authors.lastname: Heath
authors.forename: Graham J
authors.initials: GJ
authors.lastname: Lieschke
mesh_terms: D000818:Animals; D001483:Base Sequence; D019521:Body Patterning / Q000235:genetics; D002454:Cell Differentiation; D002470:Cell Survival; D018389:Codon, Nonsense; D004625:Embryo, Nonmammalian / Q000002:abnormalities / Q000473:pathology; D005804:Genes, Lethal; D006801:Humans; D022423:Myeloid Cells / Q000502:physiology*; D012322:RNA Precursors / Q000235:genetics / Q000378:metabolism; D012326:RNA Splicing; D016601:RNA-Binding Proteins / Q000235:genetics* / Q000378:metabolism; D017411:Ribonucleoproteins, Small Nuclear / Q000235:genetics / Q000378:metabolism; D017422:Sequence Analysis, DNA; D015027:Zebrafish; D029961:Zebrafish Proteins / Q000235:genetics* / Q000378:metabolism
chemical_list: D018389:Codon, Nonsense; C583218:Prpf8 protein, zebrafish; D012322:RNA Precursors; D016601:RNA-Binding Proteins; D017411:Ribonucleoproteins, Small Nuclear; D029961:Zebrafish Proteins