TY - JOUR
T1 - A bioluminescence reporter mouse that monitors expression of constitutively active β-catenin
AU - Szwarc, Maria M.
AU - Kommagani, Ramakrishna
AU - Peavey, Mary C.
AU - Hai, Lan
AU - Lonard, David M.
AU - Lydon, John P.
N1 - Funding Information:
The authors thank Jie Li, Yan Ying, and Rong Zhao for their technical expertise and the Genetically Engineered Mouse Core at Baylor College of Medicine for its mouse embryo microinjection services (Cancer Center Grant (P30 CA125123) Knockout Mouse Project; (KOMP3) Grant (U42 HG006352)). This project was supported by the Mouse Phenotyping Core at Baylor College of Medicine with funding from the NIH (U54 HG006348). We also thank Dr. Lewis A. Chodosh (Department of Cancer Biology, Abramson Family Cancer Research Institute, University of Pennsylvania School of Medicine, Philadelphia, PA) for providing the TMILA (7.4kb) cloning vector and the MTB effector mouse. This research was funded in part by: a Cancer Prevention Research Institute of Texas pre-doctoral fellowship grant (CPRIT: RP101499 (to MMS)); a Baylor College of Medicine Reproductive Endocrinology and Infertility Fellowship (to M.C.P.); a National Institutes of Health (NIH)/ National Institute of Child Health and Human Development (NICHD) grant (U01: HD-076596 (to D.M.L.)); a NIH/NICHD K99 HD080742 to RK; and a NIH/NICHD: R01: HD-042311 grant (to J.P.L.).
Publisher Copyright:
© 2017 Szwarc et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
PY - 2017/3/1
Y1 - 2017/3/1
N2 - This short technical report describes the generation and characterization of a bioluminescence reporter mouse that is engineered to detect and longitudinally monitor the expression of doxycycline-induced constitutively active β-catenin. The new responder transgenic mouse contains the TetO-ΔN89β-CatTMILA transgene, which consists of the tet-operator followed by a bicistronic sequence encoding a stabilized form of active β-catenin (ΔN89β-catenin), an internal ribosome entry site, and the firefly luciferase gene. To confirm that the transgene operates as designed, TetO-ΔN89β-CatTMILA transgenic mouse lines were crossed with an effector mouse that harbors the mouse mammary tumor virus-reverse tetracycline transactivator (MMTV-rtTA) transgene (termed MTB hereon), which primarily targets rtTA expression to the mammary epithelium. Following doxycycline administration, the resultant MTB/CatTMILA bigenic reporter exhibited precocious lobuloalveologenesis, ductal hyperplasia, and mammary adenocarcinomas, which were visualized and monitored by in vivo bioluminescence detection. Therefore, we predict that the TetO-ΔN89β-CatTMILA transgenic responder mouse - when crossed with the appropriate effector transgenic - will have wide-applicability to non-invasively monitor the influence of constitutively active β-catenin expression on cell-fate specification, proliferation, differentiation, and neoplastic transformation in a broad spectrum of target tissues.
AB - This short technical report describes the generation and characterization of a bioluminescence reporter mouse that is engineered to detect and longitudinally monitor the expression of doxycycline-induced constitutively active β-catenin. The new responder transgenic mouse contains the TetO-ΔN89β-CatTMILA transgene, which consists of the tet-operator followed by a bicistronic sequence encoding a stabilized form of active β-catenin (ΔN89β-catenin), an internal ribosome entry site, and the firefly luciferase gene. To confirm that the transgene operates as designed, TetO-ΔN89β-CatTMILA transgenic mouse lines were crossed with an effector mouse that harbors the mouse mammary tumor virus-reverse tetracycline transactivator (MMTV-rtTA) transgene (termed MTB hereon), which primarily targets rtTA expression to the mammary epithelium. Following doxycycline administration, the resultant MTB/CatTMILA bigenic reporter exhibited precocious lobuloalveologenesis, ductal hyperplasia, and mammary adenocarcinomas, which were visualized and monitored by in vivo bioluminescence detection. Therefore, we predict that the TetO-ΔN89β-CatTMILA transgenic responder mouse - when crossed with the appropriate effector transgenic - will have wide-applicability to non-invasively monitor the influence of constitutively active β-catenin expression on cell-fate specification, proliferation, differentiation, and neoplastic transformation in a broad spectrum of target tissues.
UR - http://www.scopus.com/inward/record.url?scp=85014225051&partnerID=8YFLogxK
U2 - 10.1371/journal.pone.0173014
DO - 10.1371/journal.pone.0173014
M3 - Article
C2 - 28253313
AN - SCOPUS:85014225051
VL - 12
JO - PLoS ONE
JF - PLoS ONE
SN - 1932-6203
IS - 3
M1 - e0173014
ER -