Selective reduction in microglia density and function in the white matter of colony-stimulating factor-1-deficient mice.
It is still debated whether microglia play a beneficial or harmful role in myelin disorders such as multiple sclerosis and leukodystrophies as well as in other pathological conditions of the central nervous system. The osteopetrotic (op/op) mouse has reduced numbers of cells of monocyte lineage as a result of an inactivating mutation in the colony stimulating factor-1 gene. To determine whether this mutant mouse might be used to study the role of microglia in myelin disorders, we quantified the number of microglia in the central nervous system of op/op mice and explored their ability to respond to brain injury created by a stab wound. Microglial density in the 2-month-old op/op mice was significantly decreased in the white matter tracts compared with the -ge matched wild-type controls (by 63.6% in the corpus callosum and 86.4% in the spinal dorsal column), whereas the decrease was less in the gray matter, cerebral cortex (24.0%). A similar decrease was seen at 7 months of age. Morphometric studies of spinal cord myelination showed that development of myelin was not affected in op/op mice. In response to a stab wound, the increase in the number of microglia/macrophages in op/op mice was significantly less pronounced than that in wild-type control. These findings demonstrate that this mutant is a valuable model in which to study roles of microglia/macrophages in the pathophysiology of myelin disorders.
Kondo
Yoichi
Y
Department of Medical Sciences, School of Veterinary Medicine, University of Wisconsin-Madison, Madison, Wisconsin, USA. kondoy@svm.vetmed.wisc.edu
Duncan
Ian D
ID
D000818:Animals; D001930:Brain Injuries / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology; D002452:Cell Count; D019070:Cell Lineage / Q000235:genetics; D049109:Cell Proliferation; D003337:Corpus Callosum / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D003711:Demyelinating Diseases / Q000235:genetics / Q000378:metabolism* / Q000503:physiopathology; D004195:Disease Models, Animal; D015536:Down-Regulation / Q000502:physiology; D005911:Gliosis / Q000235:genetics / Q000378:metabolism* / Q000503:physiopathology; D016173:Macrophage Colony-Stimulating Factor / Q000172:deficiency* / Q000235:genetics; D008264:Macrophages / Q000378:metabolism; D051379:Mice; D008818:Mice, Neurologic Mutants; D017628:Microglia / Q000378:metabolism*; D009413:Nerve Fibers, Myelinated / Q000378:metabolism*; D013116:Spinal Cord / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology
D016173:Macrophage Colony-Stimulating Factor