Researchers at The University of Nebraska Medical Center have developed a Janus Kinase 2 (Jak2) conditional knockout mouse. The mating of a conditional Jak2 mouse with an MMTV-Cre strain has resulted in the excision of the first coding exon of the Jak2 alleles that contains the transcriptional start codon thus creating a Jak2 null mutation. Utilizing this technology, the developers have shown that murine Jak2-/- embryos express no detectable Jak2 or phosphorylated STAT5 protein, and die at day 12.5 of gestation do to the lack of erythropoiesis, supporting the requirement for Jak2-STAT5 in EPO signaling. In addition, the mating of the Jak2 conditional knockout with the Wap- Cre transgenic mouse strain led to the inhibition of STAT5 activation in response to PRL stimulation in mammary epithelial cells. Janus Kinases show pleiotropic biological functions, and are known to participate in multiple cytokine and hormone receptor signal transduction pathways. Future work using this unique Jak2 conditional knockout mouse will allow for increased understanding of signaling events dependent upon Jak2 and its downstream effector molecules.

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