title: Generation and phenotypic analysis of sigma receptor type I (sigma 1) knockout mice.
abstract: 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 (sigma 1) has been cloned. To uncover the in vivo relevance of sigma-receptors, we have generated knockout mice for sigma 1. Despite the broad expression pattern found for the sigma 1-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 sigma 1-receptors in the induction of psychostimulant actions. The activity of sigma 2-receptors seems to be unaffected in sigma 1-mutant mice. These knockout mice could contribute to better understand the in vivo role of sigma-receptors.
authors: Centro Nacional de Biotechnología (CNB-CSIC), Department of Molecular and Cellular Biology, Campus de Cantoblanco, 28049 Madrid, Spain.
authors: Francina
authors: F
authors: Langa
authors: Xavier
authors: X
authors: Codony
authors: Victoria
authors: V
authors: Tovar
authors: Alfonso
authors: A
authors: Lavado
authors: Estela
authors: E
authors: Giménez
authors: Patricia
authors: P
authors: Cozar
authors: Marta
authors: M
authors: Cantero
authors: Albert
authors: A
authors: Dordal
authors: Enric
authors: E
authors: Hernández
authors: Raquel
authors: R
authors: Pérez
authors: Xavier
authors: X
authors: Monroy
authors: Daniel
authors: D
authors: Zamanillo
authors: Xavier
authors: X
authors: Guitart
authors: Lluís
authors: L
authors: Montoliu
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D000928:Antidepressive Agents / Q000494:pharmacology; D014150:Antipsychotic Agents / Q000494:pharmacology; D001522:Behavior, Animal; D001667:Binding, Competitive; D015152:Blotting, Northern / Q000379:methods; D015139:Blotting, Southern / Q000379:methods; D015153:Blotting, Western / Q000379:methods; D001835:Body Weight; D002478:Cells, Cultured; D004622:Embryo, Mammalian / Q000166:cytology / Q000378:metabolism; D004723:Endorphins / Q000494:pharmacology; D006579:Heterozygote; D006948:Hyperkinesis / Q000139:chemically induced / Q000378:metabolism; D017403:In Situ Hybridization / Q000379:methods; D051379:Mice; D018345:Mice, Knockout; D009292:Narcotic Antagonists / Q000378:metabolism; D016376:Oligonucleotides, Antisense / Q000378:metabolism; D010423:Pentazocine / Q000378:metabolism; D010446:Peptide Fragments / Q000494:pharmacology; D010620:Phenazocine / Q000031:analogs & derivatives* / Q000494:pharmacology; D010641:Phenotype; D011869:Radioligand Assay / Q000379:methods; D017480:Receptors, sigma / Q000235:genetics* / Q000378:metabolism; D013997:Time Factors; D000097605:Sigma-1 Receptor
chemical_list: D000928:Antidepressive Agents; D014150:Antipsychotic Agents; D004723:Endorphins; D009292:Narcotic Antagonists; D016376:Oligonucleotides, Antisense; D010423:Pentazocine; D010446:Peptide Fragments; D010620:Phenazocine; D017480:Receptors, sigma; D000097605:Sigma-1 Receptor; C018903:gamma-endorphin, des-Tyr(1)-; C012134:SK&F 10047