ANALYSIS OF NEURONAL AND GLIAL PHENOTYPES IN BRAINS OF MICE DEFICIENTIN LEUKEMIA INHIBITORY FACTOR

Leukemia inhibitory factor (LIF) can regulate the survival and differe ntiation of certain neurons and glial cells in culture. To determine t he role of this cytokine in the central nervous system in vivo, we exa mined the brains of young and adult mice in which the LIF gene was dis rupted. Immunohistochemical staining of neurons for choline acetyltran sferase, tyrosine hydroxylase, serotonin, parvalbumin, calbindin, neur opeptide Y, vasoactive intestinal polypeptide, and calcitonin gene-rel ated peptide revealed no significant differences between null mutant a nd wild-type (WT) brains. In contrast, analysis of glial phenotypes de monstrated 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 hippo campus in the female mutant is much lower than in the WT. The null mal e 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 a ddition, quantification of immunohistochemical staining of female, but not male, mutants reveals a significant deficit in myelin basic prote in content in three brain regions, suggesting alterations in oligodend rocytes as well. Thus, while overall brain histology appears normal, t he absence of LIF irt vivo leads to specific, sexually dimorphic alter ations in glial phenotype. (C) 1998 John Wiley & Sons, Inc.