Mouse model for ablation of proliferating microglia in acute CNS injuries

Glia. 2006 Feb;53(3):331-7. doi: 10.1002/glia.20288.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antimetabolites / pharmacology
  • Axotomy
  • Brain Injuries / pathology*
  • CD11b Antigen / genetics
  • Cell Proliferation
  • DNA / biosynthesis
  • DNA / genetics
  • Disease Models, Animal
  • Ganciclovir / pharmacology
  • Herpesvirus 1, Human / enzymology
  • Herpesvirus 1, Human / genetics
  • Hypoglossal Nerve / pathology
  • Immunohistochemistry
  • In Situ Hybridization
  • Mice
  • Mice, Transgenic
  • Microglia / pathology*
  • Reverse Transcriptase Polymerase Chain Reaction
  • Thymidine Kinase / genetics
  • Wounds, Stab / pathology

Substances

  • Antimetabolites
  • CD11b Antigen
  • DNA
  • Thymidine Kinase
  • Ganciclovir