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Analysis of Neuronal and Glial Phenotypes in Brains of Mice Deficient in Leukemia Inhibitory Factor

Bugga, Lakshmi and Gadient, Reto A. and Kwan, Karen and Stewart, Colin L. and Patterson, Paul H. (1998) Analysis of Neuronal and Glial Phenotypes in Brains of Mice Deficient in Leukemia Inhibitory Factor. Journal of Neurobiology, 36 (4). pp. 509-524. ISSN 0022-3034. doi:10.1002/(SICI)1097-4695(19980915)36:4<509::AID-NEU5>3.0.CO;2-#.

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Leukemia inhibitory factor (LIF) can regulate the survival and differentiation of certain neurons and glial cells in culture. To determine the role of this cytokine in the central nervous system in vivo, we examined the brains of young and adult mice in which the LIF gene was disrupted. Immunohistochemical staining of neurons for choline acetyltransferase, tyrosine hydroxylase, serotonin, parvalbumin, calbindin, neuropeptide Y, vasoactive intestinal polypeptide, and calcitonin gene-related peptide revealed no significant differences between null mutant and wild-type (WT) brains. In contrast, analysis of glial phenotypes demonstrated striking deficits in the LIF-knockout brain. Staining with several anti-glial fibrillary acidic protein (GFAP) antibodies showed that the number of GFAP-positive cells in various regions of the hippocampus in the female mutant is much lower than in the WT. The null male hippocampus also displays a significant, though less marked deficit. The number of astrocytes in the mutant hippocampus, as determined by S-100 staining, is not, however, significantly different from WT. In addition, quantification of immunohistochemical staining of female, but not male, mutants reveals a significant deficit in myelin basic protein content in three brain regions, suggesting alterations in oligodendrocytes as well. Thus, while overall brain histology appears normal, the absence of LIF in vivo leads to specific, sexually dimorphic alterations in glial phenotype.

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Additional Information:© 1998 John Wiley & Sons, Inc. Received 11 February 1997; accepted 5 May 1997. The authors thank Karen Allendoerfer, Lisa Banner, and Joanna Jankowsky for their comments on the manuscript, and Doreen McDowell for help with several aspects of the work. This research was supported by an NINDS grant to PHP, fellowships from the Swiss National Science Foundation and the Roche Research Foundation to RAG, and funding to CLS from the National Cancer Institute, under contract with ABL.
Funding AgencyGrant Number
National Institute of Neurological Disorders and Stroke (NINDS)UNSPECIFIED
Swiss National Science Foundation (SNSF)UNSPECIFIED
Roche Research FoundationUNSPECIFIED
National Cancer InstituteUNSPECIFIED
Subject Keywords:gp130; IL-6; CNTF; LIF; cytokine; sexual dimorphism
Issue or Number:4
Record Number:CaltechAUTHORS:20160331-150934424
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Official Citation:Bugga, L., Gadient, R. A., Kwan, K., Stewart, C. L. and Patterson, P. H. (1998), Analysis of neuronal and glial phenotypes in brains of mice deficient in leukemia inhibitory factor. J. Neurobiol., 36: 509–524. doi: 10.1002/(SICI)1097-4695(19980915)36:4<509::AID-NEU5>3.0.CO;2-#
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:65815
Deposited By: Ruth Sustaita
Deposited On:31 Mar 2016 22:20
Last Modified:10 Nov 2021 23:49

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