In vivo mutation of pre-mRNA processing factor 8 (Prpf8) affects transcript splicing, cell survival and myeloid differentiation

Maria-Cristina Keightley, Meredith Crowhurst, Judith E Layton, Traude Helene Beilharz, Sebastian J Markmiller, Sony Varma, Benjamin M Hogan, Tanya A de Jong-Curtain, Joan K Heath, Graham Lieschke

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33 Citations (Scopus)

Abstract

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.
Original languageEnglish
Pages (from-to)2150 - 2157
Number of pages8
JournalFEBS Letters
Volume587
Issue number14
DOIs
Publication statusPublished - 2013

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