Generation of Janus kinase 1 (JAK1) conditional knockout mice

Kazuhito Sakamoto, Barbara L. Wehde, Patrick D. Rädler, Aleata A. Triplett, Kay Uwe Wagner

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

The biological functions of the Janus kinase 1 (JAK1) are suggested to be pleiotropic since this signal transducer is ubiquitously expressed and coupled to a variety of cytokine receptors. Consequently, mice that are deficient in this tyrosine kinase were reported to die shortly after birth. To facilitate studies that address the biological and molecular functions of JAK1 during postnatal development, we performed gene targeting in embryonic stem cells and generated a Cre/lox-based conditional knockout mouse model. Expression of Cre recombinase in the germline converted the Jak1 conditional knockout allele (Jak1 fl ) into a null allele (Jak1 - ) that when subsequently crossed into homozygosity led to a complete absence of the JAK1 protein in developing embryos. JAK1 deficient embryos were visibly smaller starting at E15.5. Newborn pups exhibited signs of apnea and died within hours after birth. The examination of fibroblasts from conditional knockout embryos and their littermate wildtype controls expressing JAK1 showed that lack of this Janus kinase resulted in an impaired tyrosine phosphorylation and activation of the downstream Signal Transducers and Activators of Transcription (STATs) 1, 3, and 6. JAK1 conditional knockout mice will be an invaluable tool to study cytokine signaling during normal development and disease progression in adult animals.

Original languageEnglish (US)
Pages (from-to)582-588
Number of pages7
JournalGenesis
Volume54
Issue number11
DOIs
StatePublished - Nov 1 2016

Fingerprint

Janus Kinase 1
Knockout Mice
Embryonic Structures
STAT6 Transcription Factor
Alleles
Parturition
STAT1 Transcription Factor
Janus Kinases
STAT3 Transcription Factor
Cytokine Receptors
Gene Targeting
Apnea
Embryonic Stem Cells
Transducers
Protein-Tyrosine Kinases
Tyrosine
Disease Progression
Fibroblasts
Phosphorylation
Cytokines

Keywords

  • Cre recombinase
  • Janus kinase 1
  • STAT
  • embryonic development
  • gene targeting
  • signal transduction

ASJC Scopus subject areas

  • Genetics
  • Endocrinology
  • Cell Biology

Cite this

Sakamoto, K., Wehde, B. L., Rädler, P. D., Triplett, A. A., & Wagner, K. U. (2016). Generation of Janus kinase 1 (JAK1) conditional knockout mice. Genesis, 54(11), 582-588. https://doi.org/10.1002/dvg.22982

Generation of Janus kinase 1 (JAK1) conditional knockout mice. / Sakamoto, Kazuhito; Wehde, Barbara L.; Rädler, Patrick D.; Triplett, Aleata A.; Wagner, Kay Uwe.

In: Genesis, Vol. 54, No. 11, 01.11.2016, p. 582-588.

Research output: Contribution to journalArticle

Sakamoto, K, Wehde, BL, Rädler, PD, Triplett, AA & Wagner, KU 2016, 'Generation of Janus kinase 1 (JAK1) conditional knockout mice', Genesis, vol. 54, no. 11, pp. 582-588. https://doi.org/10.1002/dvg.22982
Sakamoto K, Wehde BL, Rädler PD, Triplett AA, Wagner KU. Generation of Janus kinase 1 (JAK1) conditional knockout mice. Genesis. 2016 Nov 1;54(11):582-588. https://doi.org/10.1002/dvg.22982
Sakamoto, Kazuhito ; Wehde, Barbara L. ; Rädler, Patrick D. ; Triplett, Aleata A. ; Wagner, Kay Uwe. / Generation of Janus kinase 1 (JAK1) conditional knockout mice. In: Genesis. 2016 ; Vol. 54, No. 11. pp. 582-588.
@article{73ade235f6c848db9a671e39632a1c98,
title = "Generation of Janus kinase 1 (JAK1) conditional knockout mice",
abstract = "The biological functions of the Janus kinase 1 (JAK1) are suggested to be pleiotropic since this signal transducer is ubiquitously expressed and coupled to a variety of cytokine receptors. Consequently, mice that are deficient in this tyrosine kinase were reported to die shortly after birth. To facilitate studies that address the biological and molecular functions of JAK1 during postnatal development, we performed gene targeting in embryonic stem cells and generated a Cre/lox-based conditional knockout mouse model. Expression of Cre recombinase in the germline converted the Jak1 conditional knockout allele (Jak1 fl ) into a null allele (Jak1 - ) that when subsequently crossed into homozygosity led to a complete absence of the JAK1 protein in developing embryos. JAK1 deficient embryos were visibly smaller starting at E15.5. Newborn pups exhibited signs of apnea and died within hours after birth. The examination of fibroblasts from conditional knockout embryos and their littermate wildtype controls expressing JAK1 showed that lack of this Janus kinase resulted in an impaired tyrosine phosphorylation and activation of the downstream Signal Transducers and Activators of Transcription (STATs) 1, 3, and 6. JAK1 conditional knockout mice will be an invaluable tool to study cytokine signaling during normal development and disease progression in adult animals.",
keywords = "Cre recombinase, Janus kinase 1, STAT, embryonic development, gene targeting, signal transduction",
author = "Kazuhito Sakamoto and Wehde, {Barbara L.} and R{\"a}dler, {Patrick D.} and Triplett, {Aleata A.} and Wagner, {Kay Uwe}",
year = "2016",
month = "11",
day = "1",
doi = "10.1002/dvg.22982",
language = "English (US)",
volume = "54",
pages = "582--588",
journal = "Genesis",
issn = "1526-954X",
publisher = "Wiley-Liss Inc.",
number = "11",

}

TY - JOUR

T1 - Generation of Janus kinase 1 (JAK1) conditional knockout mice

AU - Sakamoto, Kazuhito

AU - Wehde, Barbara L.

AU - Rädler, Patrick D.

AU - Triplett, Aleata A.

AU - Wagner, Kay Uwe

PY - 2016/11/1

Y1 - 2016/11/1

N2 - The biological functions of the Janus kinase 1 (JAK1) are suggested to be pleiotropic since this signal transducer is ubiquitously expressed and coupled to a variety of cytokine receptors. Consequently, mice that are deficient in this tyrosine kinase were reported to die shortly after birth. To facilitate studies that address the biological and molecular functions of JAK1 during postnatal development, we performed gene targeting in embryonic stem cells and generated a Cre/lox-based conditional knockout mouse model. Expression of Cre recombinase in the germline converted the Jak1 conditional knockout allele (Jak1 fl ) into a null allele (Jak1 - ) that when subsequently crossed into homozygosity led to a complete absence of the JAK1 protein in developing embryos. JAK1 deficient embryos were visibly smaller starting at E15.5. Newborn pups exhibited signs of apnea and died within hours after birth. The examination of fibroblasts from conditional knockout embryos and their littermate wildtype controls expressing JAK1 showed that lack of this Janus kinase resulted in an impaired tyrosine phosphorylation and activation of the downstream Signal Transducers and Activators of Transcription (STATs) 1, 3, and 6. JAK1 conditional knockout mice will be an invaluable tool to study cytokine signaling during normal development and disease progression in adult animals.

AB - The biological functions of the Janus kinase 1 (JAK1) are suggested to be pleiotropic since this signal transducer is ubiquitously expressed and coupled to a variety of cytokine receptors. Consequently, mice that are deficient in this tyrosine kinase were reported to die shortly after birth. To facilitate studies that address the biological and molecular functions of JAK1 during postnatal development, we performed gene targeting in embryonic stem cells and generated a Cre/lox-based conditional knockout mouse model. Expression of Cre recombinase in the germline converted the Jak1 conditional knockout allele (Jak1 fl ) into a null allele (Jak1 - ) that when subsequently crossed into homozygosity led to a complete absence of the JAK1 protein in developing embryos. JAK1 deficient embryos were visibly smaller starting at E15.5. Newborn pups exhibited signs of apnea and died within hours after birth. The examination of fibroblasts from conditional knockout embryos and their littermate wildtype controls expressing JAK1 showed that lack of this Janus kinase resulted in an impaired tyrosine phosphorylation and activation of the downstream Signal Transducers and Activators of Transcription (STATs) 1, 3, and 6. JAK1 conditional knockout mice will be an invaluable tool to study cytokine signaling during normal development and disease progression in adult animals.

KW - Cre recombinase

KW - Janus kinase 1

KW - STAT

KW - embryonic development

KW - gene targeting

KW - signal transduction

UR - http://www.scopus.com/inward/record.url?scp=84991619873&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84991619873&partnerID=8YFLogxK

U2 - 10.1002/dvg.22982

DO - 10.1002/dvg.22982

M3 - Article

C2 - 27671227

AN - SCOPUS:84991619873

VL - 54

SP - 582

EP - 588

JO - Genesis

JF - Genesis

SN - 1526-954X

IS - 11

ER -