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A sex-specific reconstitution bias in the competitive CD45.1/CD45.2 congenic bone marrow transplant model

Allelic variants of the pan-haematopoietic cell marker CD45, identified as CD45.1 and CD45.2, have been established as a marker system to track haematopoietic cells following congenic mouse bone marrow transplants. Despite the frequent use of this model for studying the impact of genetic modificatio...

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Autores principales: Jafri, Salema, Moore, Stephen D., Morrell, Nicholas W., Ormiston, Mark L.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5471196/
https://www.ncbi.nlm.nih.gov/pubmed/28615666
http://dx.doi.org/10.1038/s41598-017-03784-9
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author Jafri, Salema
Moore, Stephen D.
Morrell, Nicholas W.
Ormiston, Mark L.
author_facet Jafri, Salema
Moore, Stephen D.
Morrell, Nicholas W.
Ormiston, Mark L.
author_sort Jafri, Salema
collection PubMed
description Allelic variants of the pan-haematopoietic cell marker CD45, identified as CD45.1 and CD45.2, have been established as a marker system to track haematopoietic cells following congenic mouse bone marrow transplants. Despite the frequent use of this model for studying the impact of genetic modifications on relative differentiation potential, it is now evident that a bias exists in CD45.1 versus CD45.2 cell reconstitution. While this bias has been demonstrated by reduced reconstitution potential in B cells of CD45.1 origin, differences in the development of other lymphocytes, as well as the impact of sex on this bias, remain uncertain. We performed bone marrow transplants with wild-type CD45.1 and CD45.2 donor cells, and characterised haematopoietic cell reconstitution in dual-expressing CD45.1/2 host mice. We report an increase in CD45.2 reconstitution in the bone marrow that persists in the spleen, thymus and blood. Through the use of CD45.1/2 hosts, we demonstrate the intrinsic bias towards CD45.2 reconstitution is independent of an immunogenic response to the CD45.1 epitope. Furthermore, we identify a sex-specific difference in reconstitution efficiencies, with female mice exhibiting a greater bias towards CD45.2 reconstitution than males. This work sheds new light on the limitations of the CD45.1/CD45.2 congenic system for tracking lymphocyte development.
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spelling pubmed-54711962017-06-19 A sex-specific reconstitution bias in the competitive CD45.1/CD45.2 congenic bone marrow transplant model Jafri, Salema Moore, Stephen D. Morrell, Nicholas W. Ormiston, Mark L. Sci Rep Article Allelic variants of the pan-haematopoietic cell marker CD45, identified as CD45.1 and CD45.2, have been established as a marker system to track haematopoietic cells following congenic mouse bone marrow transplants. Despite the frequent use of this model for studying the impact of genetic modifications on relative differentiation potential, it is now evident that a bias exists in CD45.1 versus CD45.2 cell reconstitution. While this bias has been demonstrated by reduced reconstitution potential in B cells of CD45.1 origin, differences in the development of other lymphocytes, as well as the impact of sex on this bias, remain uncertain. We performed bone marrow transplants with wild-type CD45.1 and CD45.2 donor cells, and characterised haematopoietic cell reconstitution in dual-expressing CD45.1/2 host mice. We report an increase in CD45.2 reconstitution in the bone marrow that persists in the spleen, thymus and blood. Through the use of CD45.1/2 hosts, we demonstrate the intrinsic bias towards CD45.2 reconstitution is independent of an immunogenic response to the CD45.1 epitope. Furthermore, we identify a sex-specific difference in reconstitution efficiencies, with female mice exhibiting a greater bias towards CD45.2 reconstitution than males. This work sheds new light on the limitations of the CD45.1/CD45.2 congenic system for tracking lymphocyte development. Nature Publishing Group UK 2017-06-14 /pmc/articles/PMC5471196/ /pubmed/28615666 http://dx.doi.org/10.1038/s41598-017-03784-9 Text en © The Author(s) 2017 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle Article
Jafri, Salema
Moore, Stephen D.
Morrell, Nicholas W.
Ormiston, Mark L.
A sex-specific reconstitution bias in the competitive CD45.1/CD45.2 congenic bone marrow transplant model
title A sex-specific reconstitution bias in the competitive CD45.1/CD45.2 congenic bone marrow transplant model
title_full A sex-specific reconstitution bias in the competitive CD45.1/CD45.2 congenic bone marrow transplant model
title_fullStr A sex-specific reconstitution bias in the competitive CD45.1/CD45.2 congenic bone marrow transplant model
title_full_unstemmed A sex-specific reconstitution bias in the competitive CD45.1/CD45.2 congenic bone marrow transplant model
title_short A sex-specific reconstitution bias in the competitive CD45.1/CD45.2 congenic bone marrow transplant model
title_sort sex-specific reconstitution bias in the competitive cd45.1/cd45.2 congenic bone marrow transplant model
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5471196/
https://www.ncbi.nlm.nih.gov/pubmed/28615666
http://dx.doi.org/10.1038/s41598-017-03784-9
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