Mouse model for ablation of proliferating microglia in acute CNS injuries.
Activation of microglia, the primary immune effectors of the CNS and proinflammatory signaling, is a hallmark of brain damage. However, it remains controversial whether microglial cells have beneficial or detrimental functions in various neuropathological conditions. We report the generation of transgenic mice that express a mutant form of herpes simplex virus type 1 thymidine kinase (HSV-1 TK(mt-30)) driven by the myeloid-specific CD11b promoter. Using two paradigms of nervous system damage, hypoglossal nerve axotomy, and cortical stab injury, we show that specific ablation of proliferating microglia in CD11b-TK(mt-30) mice can be achieved by administration of ganciclovir. For example, after hypoglossal nerve injury, a 75% reduction in proliferating microglial cells was observed at the site of injury. The CD11b-TK(mt-30) transgenic mouse should provide a valuable tool for studying the role of microglia in CNS damage and repair.
Gowing
Geneviève
G
Laboratory of Molecular Endocrinology, CHUL Research Center and Department of Anatomy and Physiology, Laval University, Québec, Canada.
Vallières
Luc
L
Julien
Jean-Pierre
JP
D000818:Animals; D000963:Antimetabolites / Q000494:pharmacology; D019771:Axotomy; D001930:Brain Injuries / Q000473:pathology*; D039481:CD11b Antigen / Q000235:genetics; D049109:Cell Proliferation; D004247:DNA / Q000096:biosynthesis / Q000235:genetics; D004195:Disease Models, Animal; D015774:Ganciclovir / Q000494:pharmacology; D018259:Herpesvirus 1, Human / Q000201:enzymology / Q000235:genetics; D007002:Hypoglossal Nerve / Q000473:pathology; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D051379:Mice; D008822:Mice, Transgenic; D017628:Microglia / Q000473:pathology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013937:Thymidine Kinase / Q000235:genetics; D014951:Wounds, Stab / Q000473:pathology
D000963:Antimetabolites; D039481:CD11b Antigen; D004247:DNA; D013937:Thymidine Kinase; D015774:Ganciclovir