Journal article

A hypermorphic epithelial beta-catenin mutation facilitates intestinal tumorigenesis in mice in response to compounding WNT-pathway mutations

Michael Buchert, Franziska Rohde, Moritz Eissmann, Niall Tebbutt, Ben Williams, Chin Wee Tan, Alexander Owen, Yumiko Hirokawa, Alexandra Gnann, Gertraud Orend, Gayle Orner, Rod H Dashwood, Joan K Heath, Matthias Ernst, Klaus-Peter Janssen

Disease Models & Mechanisms | COMPANY BIOLOGISTS LTD | Published : 2015

Abstract

Activation of the Wnt/β-catenin pathway occurs in the vast majority of colorectal cancers. However, the outcome of the disease varies markedly from individual to individual, even within the same tumor stage. This heterogeneity is governed to a great extent by the genetic make-up of individual tumors and the combination of oncogenic mutations. In order to express throughout the intestinal epithelium a degradation-resistant β-catenin (Ctnnb1), which lacks the first 131 amino acids, we inserted an epitope-tagged ΔN(1-131)-β-catenin-encoding cDNA as a knock-in transgene into the endogenous gpA33 gene locus in mice. The resulting gpA33(ΔN-Bcat) mice showed an increase in the constitutive Wnt/β-ca..

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Funding Acknowledgements

The work in the laboratory of M.E. is supported by the Ludwig Institute for Cancer Research, the Victorian State Government Operational Infrastructure Support, the IRIISS scheme of the National Health and Medical Research Council Australia (NHMRC), and NHMRC grants #487922, #433617, #603122 and #1064987 (to M.B. and M.E.). M.E. is an NHMRC Senior Research Fellow. R.H.D. is supported by NIH P01 grant CA090890 and a Chancellor's Research Initiative from Texas A&M. Work in the laboratory of K.-P.J. is supported by grants from the Wilhelm Sander-Stiftung, the KKF (Kommission fuer klinische Forschung, Medical Faculty, TUM), and by a grant from DAAD/INCA Joint Translational Research Program on Cancer (to G. Orend. and K.-P. J.).