β-catenin and γ-catenin are dispensable for T lymphocytes and AML leukemic stem cells
- Hackensack University Medical Center, United States
- University of Iowa, United States
Abstract
The β-catenin transcriptional coregulator is involved in various biological and pathological processes; however, its requirements in hematopoietic cells remain controversial. We re-targeted the Ctnnb1 gene locus to generate a true β-catenin-null mutant mouse strain. Ablation of β-catenin alone, or in combination with its homologue γ-catenin, did not affect thymocyte maturation, survival or proliferation. Deficiency in β/γ-catenin did not detectably affect differentiation of CD4+ T follicular helper cells or that of effector and memory CD8+ cytotoxic cells in response to acute viral infection. In an MLL-AF9 AML mouse model, genetic deletion of β-catenin, or even all four Tcf/Lef family transcription factors that interact with β-catenin, did not affect AML onset in primary recipients, or the ability of leukemic stem cells (LSCs) in propagating AML in secondary recipients. Our data thus clarify on a long-standing controversy and indicate that β-catenin is dispensable for T cells and AML LSCs.
Data availability
Source data files provided. Mouse strain will be made available to other investigators upon publication of this work.
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Author details
Funding
National Institute of Allergy and Infectious Diseases (AI121080)
- Hai-Hui Xue
National Institute of Allergy and Infectious Diseases (AI139874)
- Hai-Hui Xue
U.S. Department of Veterans Affairs (BX002903)
- Hai-Hui Xue
National Institute of Allergy and Infectious Diseases (AI112579)
- Hai-Hui Xue
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Ethics
Animal experimentation: All mouse experiments were performed under protocols approved by the Institutional Animal Use and Care Committees of the University of Iowa and the Hackensack University Medical Center(Protocol No. 8021178) and Center for Discovery and Innovation, Hackensack University Medical Center (Protocol No. 276.00).
Copyright
© 2020, Zhao et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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β-catenin and γ-catenin are dispensable for T lymphocytes and AML leukemic stem cells
eLife 9:e55360.
https://doi.org/10.7554/eLife.55360
