Metabotropic glutamate receptor subtype-1 is essential for motor coordination in the adult cerebellum

Neurosci Res. 2007 Apr;57(4):538-43. doi: 10.1016/j.neures.2006.12.014. Epub 2007 Jan 7.

Abstract

We previously demonstrated that metabotropic glutamate receptor-subtype 1 knockout [mGluR1 (-/-)] mice showed ataxic gait, deficient long-term depression and impaired synapse elimination and these phenotypes were rescued by introduction of an mGluR1 transgene with Purkinje cell-specific promoter (mGluR1-rescue mice). However, roles of mGluR1 in the adult brain remain elusive, mainly due to lack of conventional and reproducible method to block mGluR1 expression at a certain developmental stage. Here, we established a versatile mouse line, mGluR1 conditional knockout (cKO) mice using the tetracycline-controlled gene expression system to understand the roles of mGluR1 in the adult brain. The mGluR1 cKO mice express mGluR1 only in Purkinje cells and show normal motor coordination. Blockade of expression of mGluR1 in the adult mGluR1 cKO mice led to impaired motor coordination, suggesting that mGluR1 is essential for cerebellar function in mice not only during postnatal development but also in adulthood.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Anti-Bacterial Agents / pharmacology
  • Behavior, Animal
  • Cerebellum / physiology*
  • Doxycycline / pharmacology
  • Gene Expression / drug effects
  • Mice
  • Mice, Knockout
  • Motor Activity / drug effects
  • Motor Activity / genetics
  • Mutation / physiology
  • Psychomotor Performance / drug effects
  • Psychomotor Performance / physiology*
  • Receptors, Metabotropic Glutamate / deficiency
  • Receptors, Metabotropic Glutamate / physiology*

Substances

  • Anti-Bacterial Agents
  • Receptors, Metabotropic Glutamate
  • metabotropic glutamate receptor type 1
  • Doxycycline