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Essential cell-extrinsic requirement for PDIA6 in lymphoid and myeloid development
In a forward genetic screen of N-ethyl-N-nitrosourea (ENU)–induced mutant mice for aberrant immune function, we identified mice with a syndromic disorder marked by growth retardation, diabetes, premature death, and severe lymphoid and myeloid hypoplasia together with diminished T cell–independent (T...
Autores principales: | , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Rockefeller University Press
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7144532/ https://www.ncbi.nlm.nih.gov/pubmed/31985756 http://dx.doi.org/10.1084/jem.20190006 |
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author | Choi, Jin Huk Zhong, Xue Zhang, Zhao Su, Lijing McAlpine, William Misawa, Takuma Liao, Tzu-Chieh Zhan, Xiaoming Russell, Jamie Ludwig, Sara Li, Xiaohong Tang, Miao Anderton, Priscilla Moresco, Eva Marie Y. Beutler, Bruce |
author_facet | Choi, Jin Huk Zhong, Xue Zhang, Zhao Su, Lijing McAlpine, William Misawa, Takuma Liao, Tzu-Chieh Zhan, Xiaoming Russell, Jamie Ludwig, Sara Li, Xiaohong Tang, Miao Anderton, Priscilla Moresco, Eva Marie Y. Beutler, Bruce |
author_sort | Choi, Jin Huk |
collection | PubMed |
description | In a forward genetic screen of N-ethyl-N-nitrosourea (ENU)–induced mutant mice for aberrant immune function, we identified mice with a syndromic disorder marked by growth retardation, diabetes, premature death, and severe lymphoid and myeloid hypoplasia together with diminished T cell–independent (TI) antibody responses. The causative mutation was in Pdia6, an essential gene encoding protein disulfide isomerase A6 (PDIA6), an oxidoreductase that functions in nascent protein folding in the endoplasmic reticulum. The immune deficiency caused by the Pdia6 mutation was, with the exception of a residual T cell developmental defect, completely rescued in irradiated wild-type recipients of PDIA6-deficient bone marrow cells, both in the absence or presence of competition. The viable hypomorphic allele uncovered in these studies reveals an essential role for PDIA6 in hematopoiesis, but one extrinsic to cells of the hematopoietic lineage. We show evidence that this role is in the proper folding of Wnt3a, BAFF, IL-7, and perhaps other factors produced by the extra-hematopoietic compartment that contribute to the development and lineage commitment of hematopoietic cells. |
format | Online Article Text |
id | pubmed-7144532 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | Rockefeller University Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-71445322020-10-06 Essential cell-extrinsic requirement for PDIA6 in lymphoid and myeloid development Choi, Jin Huk Zhong, Xue Zhang, Zhao Su, Lijing McAlpine, William Misawa, Takuma Liao, Tzu-Chieh Zhan, Xiaoming Russell, Jamie Ludwig, Sara Li, Xiaohong Tang, Miao Anderton, Priscilla Moresco, Eva Marie Y. Beutler, Bruce J Exp Med Brief Definitive Report In a forward genetic screen of N-ethyl-N-nitrosourea (ENU)–induced mutant mice for aberrant immune function, we identified mice with a syndromic disorder marked by growth retardation, diabetes, premature death, and severe lymphoid and myeloid hypoplasia together with diminished T cell–independent (TI) antibody responses. The causative mutation was in Pdia6, an essential gene encoding protein disulfide isomerase A6 (PDIA6), an oxidoreductase that functions in nascent protein folding in the endoplasmic reticulum. The immune deficiency caused by the Pdia6 mutation was, with the exception of a residual T cell developmental defect, completely rescued in irradiated wild-type recipients of PDIA6-deficient bone marrow cells, both in the absence or presence of competition. The viable hypomorphic allele uncovered in these studies reveals an essential role for PDIA6 in hematopoiesis, but one extrinsic to cells of the hematopoietic lineage. We show evidence that this role is in the proper folding of Wnt3a, BAFF, IL-7, and perhaps other factors produced by the extra-hematopoietic compartment that contribute to the development and lineage commitment of hematopoietic cells. Rockefeller University Press 2020-01-27 /pmc/articles/PMC7144532/ /pubmed/31985756 http://dx.doi.org/10.1084/jem.20190006 Text en © 2020 Choi et al. http://www.rupress.org/terms/https://creativecommons.org/licenses/by-nc-sa/4.0/This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms/). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 4.0 International license, as described at https://creativecommons.org/licenses/by-nc-sa/4.0/). |
spellingShingle | Brief Definitive Report Choi, Jin Huk Zhong, Xue Zhang, Zhao Su, Lijing McAlpine, William Misawa, Takuma Liao, Tzu-Chieh Zhan, Xiaoming Russell, Jamie Ludwig, Sara Li, Xiaohong Tang, Miao Anderton, Priscilla Moresco, Eva Marie Y. Beutler, Bruce Essential cell-extrinsic requirement for PDIA6 in lymphoid and myeloid development |
title | Essential cell-extrinsic requirement for PDIA6 in lymphoid and myeloid development |
title_full | Essential cell-extrinsic requirement for PDIA6 in lymphoid and myeloid development |
title_fullStr | Essential cell-extrinsic requirement for PDIA6 in lymphoid and myeloid development |
title_full_unstemmed | Essential cell-extrinsic requirement for PDIA6 in lymphoid and myeloid development |
title_short | Essential cell-extrinsic requirement for PDIA6 in lymphoid and myeloid development |
title_sort | essential cell-extrinsic requirement for pdia6 in lymphoid and myeloid development |
topic | Brief Definitive Report |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7144532/ https://www.ncbi.nlm.nih.gov/pubmed/31985756 http://dx.doi.org/10.1084/jem.20190006 |
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