Jak2 Conditional Knockout mouse models

Encoding the kinase that pairs with single-chain cytokine receptors, Jak2 is the mouse ortholog of human JAK2 and transduces signals from Epor, Mpl, Ghr, Prlr, and Ifngr, phosphorylating Stat5 in particular; its pseudokinase JH2 domain normally restrains the catalytic domain, and the Val617Phe substitution in that interface produces constitutive, ligand-independent activation that drives polycythemia vera, essential thrombocythemia, and primary myelofibrosis, with exon 12 insertions and deletions giving erythroid-restricted disease. Homozygous nulls die at mid-gestation from absent definitive erythropoiesis, so conditional deletion is mandatory, and the informative activating design is a conditional Val617Phe knockin at the endogenous locus expressed through Vav-Cre or interferon-inducible Mx1-Cre, which reproduces allele-dosage-dependent myeloproliferative phenotypes far more faithfully than transgenic overexpression. Humanization supports type I and type II JAK2 inhibitor pharmacology. Receptor pairing is largely nonredundant, so Jak1 and Tyk2 cannot rescue erythropoiesis; match allele class, dosage, and driver to the hematopoietic endpoint.

Conditional deletion of Jak2 limits the genetic change to the lineage you choose. That helps in oncology, immunology, and metabolic work where systemic loss would muddy the read. After you confirm Cre specificity, crossing to Jak2 floxed stock yields usable cohorts.