Enu Mutagenesis Identifies a Novel Platelet Phenotype in a Loss-Of-Function Jak2 Allele

Nicole M. Anderson, Mojib Javadi, Elizabeth Berndl, Zorana Berberovic, Monica L. Bailey, Kai Huang, Ann M. Flenniken, Lucy R. Osborne, S. Lee Adamson, Janet Rossant, Christin Carter-Su, Chen Wang, Kelly M. McNagny, Robert F. Paulson, Mark D. Minden, William L. Stanford, Dwayne L. Barber

Research output: Contribution to journalArticlepeer-review

3 Scopus citations

Abstract

Utilizing ENU mutagenesis, we identified a mutant mouse with elevated platelets. Genetic mapping localized the mutation to an interval on chromosome 19 that encodes the Jak2 tyrosine kinase. We identified a A3056T mutation resulting in a premature stop codon within exon 19 of Jak2 (Jak2K915X), resulting in a protein truncation and functionally inactive enzyme. This novel platelet phenotype was also observed in mice bearing a hemizygous targeted disruption of the Jak2 locus (Jak2+/-). Timed pregnancy experiments revealed that Jak2K915X/K915X and Jak2-/- displayed embryonic lethality; however, Jak2K915X/K915X embryos were viable an additional two days compared to Jak2-/- embryos. Our data suggest that perturbing JAK2 activation may have unexpected consequences in elevation of platelet number and correspondingly, important implications for treatment of hematological disorders with constitutive Jak2 activity.

Original languageEnglish (US)
Article numbere75472
JournalPloS one
Volume8
Issue number9
DOIs
StatePublished - Sep 25 2013

All Science Journal Classification (ASJC) codes

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)
  • General

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