Generation and phenotypic analysis of sigma receptor type I (σ1) knockout mice

• Published in: The European journal of neuroscience 2003-10, Vol.18 (8), p.2188-2196
• Main Authors: Langa, Francina, Codony, Xavier, Tovar, Victoria, Lavado, Alfonso, Giménez, Estela, Cozar, Patricia, Cantero, Marta, Dordal, Albert, Hernández, Enric, Pérez, Raquel, Monroy, Xavier, Zamanillo, Daniel, Guitart, Xavier, Montoliu, Lluís
• Format: Article
• Language: English
• Subjects: analgesia; Animals; Animals, Newborn; Antidepressive Agents - pharmacology; Antipsychotic Agents - pharmacology; Behavior, Animal; Binding, Competitive; Blotting, Northern - methods; Blotting, Southern - methods; Blotting, Western - methods; Body Weight; Cells, Cultured; Embryo, Mammalian - cytology; Embryo, Mammalian - metabolism; Endorphins - pharmacology; gene targeting; Heterozygote; Hyperkinesis - chemically induced; Hyperkinesis - metabolism; In Situ Hybridization - methods; Mice; Mice, Knockout; Narcotic Antagonists - metabolism; Oligonucleotides, Antisense - metabolism; Pentazocine - metabolism; Peptide Fragments - pharmacology; Phenazocine - analogs & derivatives; Phenazocine - pharmacology; Phenotype; Radioligand Assay - methods; Receptors, sigma - genetics; Receptors, sigma - metabolism; schizophrenia; Sigma-1 Receptor; SKF-10 047; Time Factors
• ISSN: 0953-816X; 1460-9568
• DOI: 10.1046/j.1460-9568.2003.02950.x

Sigma (σ) sites are a type of nonopiate receptor whose role has been associated with several behaviours, including anxiety, depression, analgesia, learning processes and psychosis. Although there are several known σ receptor types, only the type I receptor (σ1) has been cloned. To uncover the in vivo relevance of σ‐receptors, we have generated knockout mice for σ1. Despite the broad expression pattern found for the σ1‐gene, homozygous mutant mice are viable, fertile and do not display any overt phenotype, compared with their wild‐type litter‐mates, in mixed genetic backgrounds. However, a significant decrease in the hypermotility response has been measured in knockout mice upon challenge with (+)SKF‐10 047, in agreement with the involvement of σ1‐receptors in the induction of psychostimulant actions. The activity of σ2‐receptors seems to be unaffected in σ1‐mutant mice. These knockout mice could contribute to better understand the in vivo role of σ‐receptors.