title: Pleiotropic effects of extended blockade of CSF1R signaling in adult mice.
abstract: We investigated the role of CSF1R signaling in adult mice using prolonged treatment with anti-CSF1R antibody. Mutation of the CSF1 gene in the op/op mouse produces numerous developmental abnormalities. Mutation of the CSF1R has an even more penetrant phenotype, including perinatal lethality, because of the existence of a second ligand, IL-34. These effects on development provide limited insight into functions of CSF1R signaling in adult homeostasis. The carcass weight and weight of several organs (spleen, kidney, and liver) were reduced in the treated mice, but overall body weight gain was increased. Despite the complete loss of Kupffer cells, there was no effect on liver gene expression. The treatment ablated OCL, increased bone density and trabecular volume, and prevented the decline in bone mass seen in female mice with age. The op/op mouse has a deficiency in pancreatic β cells and in Paneth cells in the gut wall. Only the latter was reproduced by the antibody treatment and was associated with increased goblet cell number but no change in villus architecture. Male op/op mice are infertile as a result of testosterone insufficiency. Anti-CSF1R treatment ablated interstitial macrophages in the testis, but there was no sustained effect on testosterone or LH. The results indicate an ongoing requirement for CSF1R signaling in macrophage and OCL homeostasis but indicate that most effects of CSF1 and CSF1R mutations are due to effects on development.
authors.affiliation: The Roslin Institute and Royal (Dick) School of Veterinary Studies and.
authors.forename: Kristin A
authors.initials: KA
authors.lastname: Sauter
authors.affiliation: The Roslin Institute and Royal (Dick) School of Veterinary Studies and.
authors.forename: Clare
authors.initials: C
authors.lastname: Pridans
authors.affiliation: The Roslin Institute and Royal (Dick) School of Veterinary Studies and.
authors.forename: Anuj
authors.initials: A
authors.lastname: Sehgal
authors.affiliation: Medical Research Council Centre for Reproductive Health, The Queen's Medical Research Institute, University of Edinburgh, Scotland, United Kingdom.
authors.forename: Yi Ting
authors.initials: YT
authors.lastname: Tsai
authors.affiliation: The Roslin Institute and Royal (Dick) School of Veterinary Studies and.
authors.forename: Barry M
authors.initials: BM
authors.lastname: Bradford
authors.affiliation: The Roslin Institute and Royal (Dick) School of Veterinary Studies and.
authors.forename: Sobia
authors.initials: S
authors.lastname: Raza
authors.affiliation: The Roslin Institute and Royal (Dick) School of Veterinary Studies and.
authors.forename: Lindsey
authors.initials: L
authors.lastname: Moffat
authors.affiliation: The Roslin Institute and Royal (Dick) School of Veterinary Studies and.
authors.forename: Deborah J
authors.initials: DJ
authors.lastname: Gow
authors.affiliation: The Roslin Institute and Royal (Dick) School of Veterinary Studies and.
authors.forename: Philippa M
authors.initials: PM
authors.lastname: Beard
authors.affiliation: The Roslin Institute and Royal (Dick) School of Veterinary Studies and.
authors.forename: Neil A
authors.initials: NA
authors.lastname: Mabbott
authors.affiliation: Medical Research Council Centre for Reproductive Health, The Queen's Medical Research Institute, University of Edinburgh, Scotland, United Kingdom.
authors.forename: Lee B
authors.initials: LB
authors.lastname: Smith
authors.affiliation: The Roslin Institute and Royal (Dick) School of Veterinary Studies and david.hume@roslin.ed.ac.uk.
authors.forename: David A
authors.initials: DA
authors.lastname: Hume
mesh_terms: D000375:Aging / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D000818:Animals; D005260:Female; D020397:Goblet Cells / Q000276:immunology / Q000473:pathology; D006706:Homeostasis / Q000235:genetics / Q000276:immunology*; D050417:Insulin-Secreting Cells / Q000276:immunology / Q000473:pathology; D007378:Interleukins / Q000235:genetics / Q000276:immunology; D008264:Macrophages / Q000276:immunology / Q000473:pathology; D008297:Male; D051379:Mice; D008817:Mice, Mutant Strains; D009154:Mutation; D019879:Paneth Cells / Q000276:immunology / Q000473:pathology; D016186:Receptor, Macrophage Colony-Stimulating Factor / Q000235:genetics / Q000276:immunology*; D012727:Sex Characteristics; D015398:Signal Transduction / Q000235:genetics / Q000276:immunology*; D013737:Testis / Q000276:immunology / Q000473:pathology
chemical_list: D007378:Interleukins; C552364:interleukin-34, mouse; D016186:Receptor, Macrophage Colony-Stimulating Factor
keywords: Kupffer; Paneth; bone; macrophage; osteoclast; testis