Enu mutagenesis identifies a novel platelet phenotype in a loss-of-function Jak2 allele.

Enu mutagenesis identifies a novel platelet phenotype in a loss-of-function Jak2 allele.

Blog Article

Utilizing ENU mutagenesis, we identified a mutant mouse with elevated platelets.Genetic mapping localized the mutation to an interval on chromosome 19 5 Piece Casual Dining 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 8 activation may have unexpected consequences in elevation of platelet number and correspondingly, important implications for treatment of hematological disorders with constitutive Jak2 activity.