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

Sigma (sigma) 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 sigma receptor types, only the type I receptor (sigma1) has been cloned. To uncover the in vivo relevance of sigma-receptors, we have generated knockout mice for sigma1. Despite the broad expression pattern found for the sigma1-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 sigma1-receptors in the induction of psychostimulant actions. The activity of sigma2-receptors seems to be unaffected in sigma1-mutant mice. These knockout mice could contribute to better understand the in vivo role of sigma-receptors.