Please use this identifier to cite or link to this item: http://ahro.austin.org.au/austinjspui/handle/1/19309
Title: Generation of an inducible mouse model to reversibly silence Stat3.
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
EDate: 2017-02-23
Citation: 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.
URI: http://ahro.austin.org.au/austinjspui/handle/1/19309
DOI: 10.1002/dvg.23023
ORCID: 0000-0002-6399-1177
PubMed URL: 28170160
Type: Journal Article
Research Support, Non-U.S. Gov't
Subjects: Stat3
birth defects
Cancer
gastric cancer
genetics
gut
mammal
organism
shRNA model
signaling
tissue
transcription
Appears in Collections:Journal articles

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