Enu mutagenesis identifies a novel platelet phenotype in a loss-of-function Jak2 allele.
oleh: 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
| Format: | Article |
|---|---|
| Diterbitkan: | Public Library of Science (PLoS) 2013-01-01 |
Deskripsi
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 (Jak2(K915X)), 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 Jak2(K915X/K915X) and Jak2(-/-) displayed embryonic lethality; however, Jak2(K915X/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.