title: Generation of a conditional knockout allele for the Janus kinase 2 (Jak2) gene in mice.
abstract: To study biologically relevant functions of the Janus kinase 2 (Jak2) in multiple cytokine and hormone receptor signal transduction pathways, we generated a conditional knockout (floxed) allele of this gene by placing loxP sites around the first coding exon of Jak2. Homozygous floxed animals developed normally and exhibited no phenotypic abnormalities. The conversion of the floxed allele into a null mutation was achieved by transmitting the targeted allele through the female germline of MMTV-Cre (line A) mice. Embryos that carry two Jak2 null alleles died around midgestation and exhibited impaired definitive erythropoiesis, which is a hallmark of Jak2 deficiency reported previously in conventional knockouts. This observation suggested that the Cre-mediated deletion of the first coding exon results in a true null mutation that is incapable of mediating signals through the erythropoietin receptor. Using mouse embryonic fibroblasts derived from Jak2 null embryos and their wildtype littermate controls, we demonstrated that Jak2-deficiency decouples growth hormone-receptor signaling from its downstream mediators, the signal transducer and activator of transcription (Stat) 5a and 5b.
authors.affiliation: Eppley Institute for Research in Cancer and Allied Diseases and the Department of Pathology and Microbiology, University of Nebraska Medical Center, Omaha, Nebraska 68198-6805, USA.
authors.forename: Andrea
authors.initials: A
authors.lastname: Krempler
authors.forename: Yongyue
authors.initials: Y
authors.lastname: Qi
authors.forename: Aleata A
authors.initials: AA
authors.lastname: Triplett
authors.forename: Jianqiong
authors.initials: J
authors.lastname: Zhu
authors.forename: Hallgeir
authors.initials: H
authors.lastname: Rui
authors.forename: Kay-Uwe
authors.initials: KU
authors.lastname: Wagner
mesh_terms: D000818:Animals; D004920:Erythropoiesis / Q000235:genetics; D005091:Exons / Q000235:genetics; D005260:Female; D005313:Fetal Death / Q000235:genetics; D017353:Gene Deletion; D053614:Janus Kinase 2; D008324:Mammary Tumor Virus, Mouse / Q000235:genetics; D051379:Mice; D018345:Mice, Knockout; D011247:Pregnancy; D011505:Protein-Tyrosine Kinases / Q000172:deficiency* / Q000235:genetics*; D011518:Proto-Oncogene Proteins / Q000172:deficiency* / Q000235:genetics*
chemical_list: D011518:Proto-Oncogene Proteins; D011505:Protein-Tyrosine Kinases; C507926:Jak2 protein, mouse; D053614:Janus Kinase 2