A genetically modified mouse model probing the selective action of ifenprodil at the N-methyl-D-aspartate type 2B receptor.
Mol Cell Neurosci
; 33(1): 47-56, 2006 Sep.
Article
em En
| MEDLINE
| ID: mdl-16870468
ABSTRACT
Selective antagonism of N-methyl-d-aspartate (NMDA) 2B subunit containing receptors has been suggested to have potential therapeutic application for multiple CNS disorders. The amino terminal NR2B residues 1 to 282 were found to be both necessary and sufficient for the binding and function of highly NR2B subunit specific antagonists like ifenprodil and CP-101,606. Using a genetic approach in mice, we successfully replaced the murine NR2B gene function by "knocking-in" (KI) a chimeric human NR2A/B cDNA containing the minimal domain abolishing ifenprodil binding into the endogenous NR2B locus. Patch-clamp recording from hippocampal cultures of the NR2B KI mice demonstrated that their NMDA receptors have reduced sensitivity to both ifenprodil and CP-101,606, as predicted, but also have a lower affinity for glycine. The NR2B KI mice exhibited normal locomotor activity making this ifenprodil-insensitive mouse model a valuable tool to test the specificity of NR2B selective antagonists in vivo.
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Base de dados:
MEDLINE
Assunto principal:
Piperidinas
/
Receptores de N-Metil-D-Aspartato
/
Antagonistas de Aminoácidos Excitatórios
/
Subunidades Proteicas
Idioma:
En
Ano de publicação:
2006
Tipo de documento:
Article