Projects per year
Abstract
Granulocyte colony-stimulating factor (GCSF) and its receptor (GCSFR), also known as CSF3 and CSF3R, are required to maintain normal neutrophil numbers during basal and emergency granulopoiesis in humans, mice and zebrafish. Previous studies identified two zebrafish CSF3 ligands and a single CSF3 receptor. Transient antisense morpholino oligonucleotide knockdown of both these ligands and receptor reduces neutrophil numbers in zebrafish embryos, a technique widely used to evaluate neutrophil contributions to models of infection, inflammation and regeneration. We created an allelic series of zebrafish csf3r mutants by CRISPR/Cas9 mutagenesis targeting csf3r exon 2. Biallelic csf3r mutant embryos are viable and have normal early survival, despite a substantial reduction of their neutrophil population size, and normal macrophage abundance. Heterozygotes have a haploinsufficiency phenotype with an intermediate reduction in neutrophil numbers. csf3r mutants are viable as adults, with a 50% reduction in tissue neutrophil density and a substantial reduction in the number of myeloid cells in the kidney marrow. These csf3r mutants are a new animal model of human CSF3R-dependent congenital neutropenia. Furthermore, they will be valuable for studying the impact of neutrophil loss in the context of other zebrafish disease models by providing a genetically stable, persistent, reproducible neutrophil deficiency state throughout life.
Original language | English |
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Article number | 44455 |
Number of pages | 11 |
Journal | Scientific Reports |
Volume | 7 |
DOIs | |
Publication status | Published - 10 Mar 2017 |
Projects
- 3 Finished
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Zbtb11 interactions in haematopoiesis and disease
National Health and Medical Research Council (NHMRC) (Australia)
1/01/14 → 31/12/16
Project: Research
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Cellular and molecular mechanisms of fungal infection pathogenesis and therapy
Lieschke, G. & Andrianopoulos, A.
National Health and Medical Research Council (NHMRC) (Australia)
1/01/14 → 31/12/17
Project: Research
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NHMRC Research Fellowship
National Health and Medical Research Council (NHMRC) (Australia)
1/01/07 → 31/12/17
Project: Research
Equipment
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FlowCore
Andrew Fryga (Manager)
Faculty of Medicine Nursing and Health Sciences Research PlatformsFacility/equipment: Facility
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Micromon
Scott Coutts (Manager)
Faculty of Medicine Nursing and Health Sciences Research PlatformsFacility/equipment: Facility