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Loss of Shp1 impairs myeloid cell function and causes lethal inflammation in zebrafish larvae
PTPN6 encodes SHP1, a protein tyrosine phosphatase with an essential role in immune cell function. SHP1 mutations are associated with neutrophilic dermatoses and emphysema in humans, which resembles the phenotype seen in motheaten mice that lack functional SHP1. To investigate the function of Shp1 i...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
The Company of Biologists Ltd
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9922729/ https://www.ncbi.nlm.nih.gov/pubmed/36645087 http://dx.doi.org/10.1242/dmm.049715 |
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author | Allers, Maaike Bakker, Petra A. Hoeksma, Jelmer Spaink, Herman P. den Hertog, Jeroen |
author_facet | Allers, Maaike Bakker, Petra A. Hoeksma, Jelmer Spaink, Herman P. den Hertog, Jeroen |
author_sort | Allers, Maaike |
collection | PubMed |
description | PTPN6 encodes SHP1, a protein tyrosine phosphatase with an essential role in immune cell function. SHP1 mutations are associated with neutrophilic dermatoses and emphysema in humans, which resembles the phenotype seen in motheaten mice that lack functional SHP1. To investigate the function of Shp1 in developing zebrafish embryos, we generated a ptpn6 knockout zebrafish line lacking functional Shp1. Shp1 knockout caused severe inflammation and lethality around 17 days post fertilization (dpf). During early development, the myeloid lineage was affected, resulting in a decrease in the number of neutrophils and a concomitant increase in the number of macrophages. The number of emerging hematopoietic stem and progenitor cells (HSPCs) was decreased, but due to hyperproliferation, the number of HSPCs was higher in ptpn6 mutants than in siblings at 5 dpf. Finally, the directional migration of neutrophils and macrophages was decreased in response to wounding, and fewer macrophages were recruited to the wound site. Yet, regeneration of the caudal fin fold was normal. We conclude that loss of Shp1 impaired neutrophil and macrophage function, and caused severe inflammation and lethality at the larval stage. |
format | Online Article Text |
id | pubmed-9922729 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | The Company of Biologists Ltd |
record_format | MEDLINE/PubMed |
spelling | pubmed-99227292023-02-13 Loss of Shp1 impairs myeloid cell function and causes lethal inflammation in zebrafish larvae Allers, Maaike Bakker, Petra A. Hoeksma, Jelmer Spaink, Herman P. den Hertog, Jeroen Dis Model Mech Research Article PTPN6 encodes SHP1, a protein tyrosine phosphatase with an essential role in immune cell function. SHP1 mutations are associated with neutrophilic dermatoses and emphysema in humans, which resembles the phenotype seen in motheaten mice that lack functional SHP1. To investigate the function of Shp1 in developing zebrafish embryos, we generated a ptpn6 knockout zebrafish line lacking functional Shp1. Shp1 knockout caused severe inflammation and lethality around 17 days post fertilization (dpf). During early development, the myeloid lineage was affected, resulting in a decrease in the number of neutrophils and a concomitant increase in the number of macrophages. The number of emerging hematopoietic stem and progenitor cells (HSPCs) was decreased, but due to hyperproliferation, the number of HSPCs was higher in ptpn6 mutants than in siblings at 5 dpf. Finally, the directional migration of neutrophils and macrophages was decreased in response to wounding, and fewer macrophages were recruited to the wound site. Yet, regeneration of the caudal fin fold was normal. We conclude that loss of Shp1 impaired neutrophil and macrophage function, and caused severe inflammation and lethality at the larval stage. The Company of Biologists Ltd 2023-01-30 /pmc/articles/PMC9922729/ /pubmed/36645087 http://dx.doi.org/10.1242/dmm.049715 Text en © 2023. Published by The Company of Biologists Ltd https://creativecommons.org/licenses/by/4.0/This is an Open Access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution and reproduction in any medium provided that the original work is properly attributed. |
spellingShingle | Research Article Allers, Maaike Bakker, Petra A. Hoeksma, Jelmer Spaink, Herman P. den Hertog, Jeroen Loss of Shp1 impairs myeloid cell function and causes lethal inflammation in zebrafish larvae |
title | Loss of Shp1 impairs myeloid cell function and causes lethal inflammation in zebrafish larvae |
title_full | Loss of Shp1 impairs myeloid cell function and causes lethal inflammation in zebrafish larvae |
title_fullStr | Loss of Shp1 impairs myeloid cell function and causes lethal inflammation in zebrafish larvae |
title_full_unstemmed | Loss of Shp1 impairs myeloid cell function and causes lethal inflammation in zebrafish larvae |
title_short | Loss of Shp1 impairs myeloid cell function and causes lethal inflammation in zebrafish larvae |
title_sort | loss of shp1 impairs myeloid cell function and causes lethal inflammation in zebrafish larvae |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9922729/ https://www.ncbi.nlm.nih.gov/pubmed/36645087 http://dx.doi.org/10.1242/dmm.049715 |
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