Pleiotropic effects of extended blockade of CSF1R signaling in adult mice

Sauter, Kristin A., Pridans, Clare, Sehgal, Anuj, Tsai, Yi Ting, Bradford, Barry M., Raza, Sobia, Moffat, Lindsey, Gow, Deborah J., Beard, Philippa M., Mabbott, Neil A., Smith, Lee B. and Hume, David A. (2014) Pleiotropic effects of extended blockade of CSF1R signaling in adult mice. Journal of Leukocyte Biology, 96 2: 265-274. doi:10.1189/jlb.2A0114-006R


Author Sauter, Kristin A.
Pridans, Clare
Sehgal, Anuj
Tsai, Yi Ting
Bradford, Barry M.
Raza, Sobia
Moffat, Lindsey
Gow, Deborah J.
Beard, Philippa M.
Mabbott, Neil A.
Smith, Lee B.
Hume, David A.
Title Pleiotropic effects of extended blockade of CSF1R signaling in adult mice
Journal name Journal of Leukocyte Biology   Check publisher's open access policy
ISSN 1938-3673
0741-5400
Publication date 2014-08-01
Sub-type Article (original research)
DOI 10.1189/jlb.2A0114-006R
Open Access Status Not yet assessed
Volume 96
Issue 2
Start page 265
End page 274
Total pages 10
Place of publication Chichester, West Sussex United Kingdom
Publisher John Wiley & Sons
Language eng
Formatted 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.
Keyword Bone
Kupffer
Macrophage
Osteoclast
Paneth
Testis
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status Non-UQ

Document type: Journal Article
Sub-type: Article (original research)
Collection: Mater Research Institute-UQ (MRI-UQ)
 
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Created: Fri, 20 Apr 2018, 09:35:41 EST