PUBLICATION
Loss of Shp1 impairs myeloid cell function and causes lethal inflammation in zebrafish larvae
- Authors
- Allers, M., Bakker, P.A., Hoeksma, J., Spaink, H.P., den Hertog, J.
- ID
- ZDB-PUB-230117-7
- Date
- 2023
- Source
- Disease models & mechanisms 16(2): (Journal)
- Registered Authors
- den Hertog, Jeroen, Spaink, Herman P.
- Keywords
- Macrophage, Neutrophil, Protein-tyrosine phosphatase, Shp1, Zebrafish
- MeSH Terms
-
- Animals
- Humans
- Inflammation*/genetics
- Larva
- Mice
- Myeloid Cells/metabolism
- Protein Tyrosine Phosphatase, Non-Receptor Type 6/genetics
- Protein Tyrosine Phosphatase, Non-Receptor Type 6/metabolism
- Zebrafish*/metabolism
- PubMed
- 36645087 Full text @ Dis. Model. Mech.
Citation
Allers, M., Bakker, P.A., Hoeksma, J., Spaink, H.P., den Hertog, J. (2023) Loss of Shp1 impairs myeloid cell function and causes lethal inflammation in zebrafish larvae. Disease models & mechanisms. 16(2):.
Abstract
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. We investigated 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, directional migration of neutrophils and macrophages was decreased in response to wounding and less 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.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping