1. Immunology and Inflammation
  2. Stem Cells and Regenerative Medicine
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β-catenin and γ-catenin are dispensable for T lymphocytes and AML leukemic stem cells

  1. Xin Zhao
  2. Peng Shao
  3. Kexin Gai
  4. Fengyin Li
  5. Qiang Shan
  6. Hai-Hui Xue  Is a corresponding author
  1. Hackensack University Medical Center, United States
  2. University of Iowa, United States
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Cite this article as: eLife 2020;9:e55360 doi: 10.7554/eLife.55360
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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.

Article and author information

Author details

  1. Xin Zhao

    Center for Discovery and Innovation, Hackensack University Medical Center, Nutley, United States
    Competing interests
    The authors declare that no competing interests exist.
  2. Peng Shao

    Microbiology and Immunology, University of Iowa, Iowa City, United States
    Competing interests
    The authors declare that no competing interests exist.
  3. Kexin Gai

    Center for Discovery and Innovation, Hackensack University Medical Center, Nutley, United States
    Competing interests
    The authors declare that no competing interests exist.
  4. Fengyin Li

    Microbiology and Immunology, University of Iowa, Iowa City, United States
    Competing interests
    The authors declare that no competing interests exist.
  5. Qiang Shan

    Center for Discovery and Innovation, Hackensack University Medical Center, Nutley, United States
    Competing interests
    The authors declare that no competing interests exist.
  6. Hai-Hui Xue

    Center for Discovery and Innovation, Hackensack University Medical Center, Nutley, United States
    For correspondence
    haihui.xue@hmh-cdi.org
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-9163-7669

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).

Reviewing Editor

  1. Ravi Majeti, Stanford University, United States

Publication history

  1. Received: January 21, 2020
  2. Accepted: August 14, 2020
  3. Accepted Manuscript published: August 21, 2020 (version 1)
  4. Version of Record published: September 1, 2020 (version 2)

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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