Please use this identifier to cite or link to this item:
Title: Generation of an inducible mouse model to reversibly silence Stat3.
Austin Authors: Alorro, Mariah G;Pierce, Thomas P;Eissmann, Moritz F ;Dijkstra, Christine ;Dickins, Ross A;Ernst, Matthias ;Buchert, Michael;Masson, Frederic
Affiliation: Cancer and Inflammation Laboratory, Olivia Newton-John Cancer Research Institute, Heidelberg, Victoria, Australia
School of Cancer Medicine, La Trobe University, Melbourne, Victoria, Australia
Dickins Laboratory, Australian Centre for Blood Diseases, Monash University, Melbourne, Victoria, Australia
Issue Date: 2017 2017-02-23
Publication information: Genesis 2017; 55(4)
Abstract: Signal transducer and activator of transcription 3 (Stat3) is a transcription factor that has many essential roles during inflammation, development and cancer. Stat3 is therefore an attractive therapeutic target in many diseases. While current Stat3 knockout mouse models led to a better understanding of the role of Stat3, the irreversible nature of Stat3 ablation does not model the effects of transient Stat3 therapeutic inhibition, and does not inform on potential dosage effects of Stat3. Using RNAi technology, we have generated a new mouse model allowing the inducible and reversible silencing of Stat3 in vivo, which mirrors the effects of specific Stat3 therapeutic interference. We showed that upon Doxycycline-mediated activation of the Stat3 short-hairpin RNA, Stat3 expression was efficiently reduced by about 80% in multiple organs and cell types. Moreover, Stat3 reduction was sufficient to reduce tumor burden in a clinically-validated mouse model of gastric cancer. Finally, we demonstrated that Stat3 silencing during embryonic development led to reduced birth rate without leading to complete embryonic lethality, in contrast to full Stat3 ablation. In conclusion, this new mouse model will be invaluable to understand the effects of Stat3 therapeutic interference and Stat3 dosage effects.
DOI: 10.1002/dvg.23023
ORCID: 0000-0002-6399-1177
PubMed URL: 28170160
Type: Journal Article
Subjects: Stat3
birth defects
gastric cancer
shRNA model
Appears in Collections:Journal articles

Show full item record

Page view(s)

checked on Dec 7, 2022

Google ScholarTM


Items in AHRO are protected by copyright, with all rights reserved, unless otherwise indicated.