title: Reduced STAT3 activity in mice mimics clinical disease syndromes.
abstract: 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.
authors.affiliation: Laboratory of Molecular Cell Biology, The Rockefeller University, New York 10021, USA.
authors.forename: Yuhong
authors.initials: Y
authors.lastname: Shen
authors.forename: Krista M D
authors.initials: KM
authors.lastname: La Perle
authors.forename: David E
authors.initials: DE
authors.lastname: Levy
authors.forename: James E
authors.initials: JE
authors.lastname: Darnell
mesh_terms: D000818:Animals; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D004194:Disease; D004317:Doxorubicin / Q000494:pharmacology; D006321:Heart / Q000187:drug effects / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D050796:STAT3 Transcription Factor; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism*; D014158:Transcription, Genetic
chemical_list: D004268:DNA-Binding Proteins; D050796:STAT3 Transcription Factor; C494087:Stat3 protein, mouse; D015534:Trans-Activators; D004317:Doxorubicin