Generation of a conditional knockout allele for the Janus kinase 2 (Jak2) gene in mice

Andrea Krempler, Yongyue Qi, Aleata A. Triplett, Jianqiong Zhu, Hallgeir Rui, Kay Uwe Wagner

Research output: Contribution to journalArticle

67 Scopus citations

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 IoxP 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.

Original languageEnglish (US)
Pages (from-to)52-57
Number of pages6
JournalGenesis
Volume40
Issue number1
DOIs
StatePublished - Sep 1 2004

    Fingerprint

Keywords

  • Cre recombinase
  • Embryonic development
  • Gene targeting
  • Janus kinase 2
  • Stat5

ASJC Scopus subject areas

  • Genetics
  • Endocrinology
  • Cell Biology

Cite this

Krempler, A., Qi, Y., Triplett, A. A., Zhu, J., Rui, H., & Wagner, K. U. (2004). Generation of a conditional knockout allele for the Janus kinase 2 (Jak2) gene in mice. Genesis, 40(1), 52-57. https://doi.org/10.1002/gene.20063