Generation and phenotypic analysis of sigma receptor type I (sigma 1) 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 (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.
Langa
Francina
F
Centro Nacional de Biotechnología (CNB-CSIC), Department of Molecular and Cellular Biology, Campus de Cantoblanco, 28049 Madrid, Spain.
Codony
Xavier
X
Tovar
Victoria
V
Lavado
Alfonso
A
Giménez
Estela
E
Cozar
Patricia
P
Cantero
Marta
M
Dordal
Albert
A
Hernández
Enric
E
Pérez
Raquel
R
Monroy
Xavier
X
Zamanillo
Daniel
D
Guitart
Xavier
X
Montoliu
Lluís
L
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
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