ZFIN ID: ZDB-PUB-130708-8
In vivo mutation of pre-mRNA processing factor 8 (Prpf8) affects transcript splicing, cell survival and myeloid differentiation
Keightley, M.C., Crowhurst, M.O., Layton, J.E., Beilharz, T., Markmiller, S., Varma, S., Hogan, B.M., de Jong-Curtain, T.A., Heath, J.K., and Lieschke, G.J.
Date: 2013
Source: FEBS letters   587(14): 2150-2157 (Journal)
Registered Authors: Crowhurst, Meredith, de Jong-Curtain, Tanya A., Heath, Joan K., Hogan, Ben M., Keightley, M. Cristina, Layton, Judy E., Lieschke, Graham J., Markmiller, Sebastian, Varma, Sony
Keywords: PRPF8, haematopoiesis, splicing, zebrafish, myelopoiesis, spliceosome, snRNP
MeSH Terms:
  • Animals
  • Base Sequence
  • Body Patterning/genetics
  • Cell Differentiation*
  • Cell Survival
  • Codon, Nonsense*
  • Embryo, Nonmammalian/abnormalities
  • Embryo, Nonmammalian/pathology
  • Genes, Lethal
  • Humans
  • Myeloid Cells/physiology*
  • RNA Precursors/genetics
  • RNA Precursors/metabolism
  • RNA Splicing*
  • RNA-Binding Proteins/genetics*
  • RNA-Binding Proteins/metabolism
  • Ribonucleoproteins, Small Nuclear/genetics
  • Ribonucleoproteins, Small Nuclear/metabolism
  • Sequence Analysis, DNA
  • Zebrafish
  • Zebrafish Proteins/genetics*
  • Zebrafish Proteins/metabolism
PubMed: 23714367 Full text @ FEBS Lett.

Mutated spliceosome components are recurrently being associated with perturbed tissue development and disease pathogenesis. CephalophOnus (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.