Floxed allele for conditional inactivation of the GABAB(1) gene

Genesis. 2004 Nov;40(3):125-30. doi: 10.1002/gene.20073.

Abstract

GABA(B) receptors are the G-protein-coupled receptors for the neurotransmitter GABA. GABA(B) receptors are broadly expressed in the nervous system. Their complete absence in mice causes premature lethality or--when mice are viable--epilepsy, impaired memory, hyperalgesia, hypothermia, and hyperactivity. A spatially and temporally restricted loss of GABA(B) function would allow addressing how the absence of GABA(B) receptors leads to these diverse phenotypes. To permit a conditional gene inactivation, we flanked critical exons of the GABA(B(1)) gene with lox511 sites. GABA(B(1)) (lox511/lox511) mice exhibit normal levels of GABA(B(1)) protein, are fertile, and do not display any behavioral phenotype. We crossed GABA(B(1)) (lox511/lox511) with Cre-deleter mice to produce mice with an unrestricted GABA(B) receptor elimination. These GABA(B(1)) (-/-) mice no longer synthesize GABA(B(1)) protein and exhibit the expected behavioral abnormalities. The conditional GABA(B(1)) allele described here is therefore suitable for generating mice with a site- and time-specific loss of GABA(B) function.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alleles*
  • Animals
  • Baclofen / pharmacology
  • Behavior, Animal / drug effects
  • Body Temperature Regulation / drug effects
  • Crosses, Genetic
  • Female
  • GABA Agonists / pharmacology
  • Gene Silencing / physiology*
  • Gene Targeting
  • Hypothermia / chemically induced
  • Integrases / genetics
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Mutagenesis, Insertional
  • Receptors, GABA-B / genetics*

Substances

  • GABA Agonists
  • Receptors, GABA-B
  • Cre recombinase
  • Integrases
  • Baclofen