Pleiotropic Impacts of Macrophage and Microglial Deficiency on Development in Rats with Targeted Mutation of the Csf1r Locus.

Autor:	Pridans C; The Roslin Institute, The University of Edinburgh, Easter Bush EH25 9RG, United Kingdom; clare.pridans@ed.ac.uk David.Hume@uq.edu.au.; The University of Edinburgh Centre for Inflammation Research, The Queen's Medical Research Institute, Edinburgh EH16 4TJ, United Kingdom., Raper A; The Roslin Institute, The University of Edinburgh, Easter Bush EH25 9RG, United Kingdom., Davis GM; The Roslin Institute, The University of Edinburgh, Easter Bush EH25 9RG, United Kingdom., Alves J; The Roslin Institute, The University of Edinburgh, Easter Bush EH25 9RG, United Kingdom., Sauter KA; The Roslin Institute, The University of Edinburgh, Easter Bush EH25 9RG, United Kingdom., Lefevre L; The Roslin Institute, The University of Edinburgh, Easter Bush EH25 9RG, United Kingdom., Regan T; The Roslin Institute, The University of Edinburgh, Easter Bush EH25 9RG, United Kingdom., Meek S; The Roslin Institute, The University of Edinburgh, Easter Bush EH25 9RG, United Kingdom., Sutherland L; The Roslin Institute, The University of Edinburgh, Easter Bush EH25 9RG, United Kingdom., Thomson AJ; The Roslin Institute, The University of Edinburgh, Easter Bush EH25 9RG, United Kingdom.; New World Laboratories, Laval, Quebec H7V 5B7, Canada., Clohisey S; The Roslin Institute, The University of Edinburgh, Easter Bush EH25 9RG, United Kingdom., Bush SJ; The Roslin Institute, The University of Edinburgh, Easter Bush EH25 9RG, United Kingdom.; Nuffield Department of Clinical Medicine, University of Oxford, John Radcliffe Hospital, Headington, Oxford OX3 9DU, United Kingdom., Rojo R; The Roslin Institute, The University of Edinburgh, Easter Bush EH25 9RG, United Kingdom., Lisowski ZM; The Roslin Institute, The University of Edinburgh, Easter Bush EH25 9RG, United Kingdom., Wallace R; Department of Orthopaedic Surgery, The University of Edinburgh, Edinburgh EH16 4TJ, United Kingdom., Grabert K; The Roslin Institute, The University of Edinburgh, Easter Bush EH25 9RG, United Kingdom., Upton KR; The Roslin Institute, The University of Edinburgh, Easter Bush EH25 9RG, United Kingdom.; School of Chemistry and Molecular Biosciences, The University of Queensland, Brisbane, Queensland 4072, Australia., Tsai YT; Medical Research Council Centre for Reproductive Health, The University of Edinburgh, Edinburgh EH16 4TJ, United Kingdom., Brown D; The Roslin Institute, The University of Edinburgh, Easter Bush EH25 9RG, United Kingdom., Smith LB; Medical Research Council Centre for Reproductive Health, The University of Edinburgh, Edinburgh EH16 4TJ, United Kingdom.; Faculty of Science, University of Newcastle, Callaghan, New South Wales 2309, Australia; and., Summers KM; Mater Research-University of Queensland, Brisbane, Queensland 4101, Australia., Mabbott NA; The Roslin Institute, The University of Edinburgh, Easter Bush EH25 9RG, United Kingdom., Piccardo P; The Roslin Institute, The University of Edinburgh, Easter Bush EH25 9RG, United Kingdom., Cheeseman MT; The Roslin Institute, The University of Edinburgh, Easter Bush EH25 9RG, United Kingdom., Burdon T; The Roslin Institute, The University of Edinburgh, Easter Bush EH25 9RG, United Kingdom., Hume DA; The University of Edinburgh Centre for Inflammation Research, The Queen's Medical Research Institute, Edinburgh EH16 4TJ, United Kingdom; clare.pridans@ed.ac.uk David.Hume@uq.edu.au.; Mater Research-University of Queensland, Brisbane, Queensland 4101, Australia.
Jazyk:	angličtina
Zdroj:	Journal of immunology (Baltimore, Md. : 1950) [J Immunol] 2018 Nov 01; Vol. 201 (9), pp. 2683-2699. Date of Electronic Publication: 2018 Sep 24.
DOI:	10.4049/jimmunol.1701783
Abstrakt:	We have produced Csf1r -deficient rats by homologous recombination in embryonic stem cells. Consistent with the role of Csf1r in macrophage differentiation, there was a loss of peripheral blood monocytes, microglia in the brain, epidermal Langerhans cells, splenic marginal zone macrophages, bone-associated macrophages and osteoclasts, and peritoneal macrophages. Macrophages of splenic red pulp, liver, lung, and gut were less affected. The pleiotropic impacts of the loss of macrophages on development of multiple organ systems in rats were distinct from those reported in mice. Csf1r -/- rats survived well into adulthood with postnatal growth retardation, distinct skeletal and bone marrow abnormalities, infertility, and loss of visceral adipose tissue. Gene expression analysis in spleen revealed selective loss of transcripts associated with the marginal zone and, in brain regions, the loss of known and candidate novel microglia-associated transcripts. Despite the complete absence of microglia, there was little overt phenotype in brain, aside from reduced myelination and increased expression of dopamine receptor-associated transcripts in striatum. The results highlight the redundant and nonredundant functions of CSF1R signaling and of macrophages in development, organogenesis, and homeostasis. (Copyright © 2018 The Authors.)
Databáze:	MEDLINE
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