Reduced STAT3 activity in mice mimics clinical disease syndromes

Biochem Biophys Res Commun. 2005 Apr 29;330(1):305-9. doi: 10.1016/j.bbrc.2005.02.154.


Phosphorylation on Y705 is obligatory for STAT3 activation, but full transcriptional activity of this widely expressed protein also requires phosphorylation on S727. We described earlier the STAT3 SA/- mice (SA, S727A allele) on a Black 6 (Bl6) background that showed 75% perinatal lethality and early growth retardation presumably due to the decreased transcription supported by STAT3 S727A. We now report additional analyses of long-term surviving SA/- animals which show no important tissue abnormalities. However, we have found a much greater susceptibility to doxorubicin-induced heart failure in the SA/- mice. Also we introduced the SA allele into strain 129 and found the SA/- mice showed greater susceptibility to LPS-induced toxicity. These results suggest a continued need for normal STAT3 transcriptional activity to resist two different noxious challenges that mimic the conditions necessary to induce adult diseases.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / metabolism*
  • Disease*
  • Doxorubicin / pharmacology
  • Heart / drug effects
  • Heart / physiology
  • Mice
  • Mice, Inbred C57BL
  • STAT3 Transcription Factor
  • Trans-Activators / genetics
  • Trans-Activators / metabolism*
  • Transcription, Genetic


  • DNA-Binding Proteins
  • STAT3 Transcription Factor
  • Stat3 protein, mouse
  • Trans-Activators
  • Doxorubicin