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IN PRODUCTION

Jak1, the mouse ortholog of human JAK1, encodes a nonreceptor tyrosine kinase organized into a FERM domain, an SH2-like module, a catalytically inactive pseudokinase that autoinhibits, and the active kinase domain; it docks on box1 and box2 motifs of type I and type II interferon receptors, gp130-family receptors, and gamma-common cytokine receptors, then phosphorylates receptor tails and Stat1, Stat3, and Stat5 to license dimerization and nuclear import. Homozygous nulls die perinatally with failure to nurse and neurological deficits, so conditional deletion is required for immune and tumor studies, while pseudokinase-domain activating knockins found in acute lymphoblastic leukemia test ligand-independent signaling and kinase-dead alleles separate catalysis from receptor scaffolding. Humanization is the design that supports selectivity profiling of JAK1-biased inhibitors, since paralog-specific pharmacology is the central question. Jak2, Jak3, and Tyk2 pair with distinct receptor chains and do not broadly substitute, though shared receptor complexes can blunt single-gene phenotypes.

A floxed Jak1 allele paired with Cre gives spatial control that whole body knockouts cannot offer. People use it to separate developmental roles from adult homeostasis, to model somatic mutations, and to match disease that begins in one organ.