A Hypomorphic Vasopressin Allele Prevents Anxiety-Related Behavior

摘要: Background To investigate neurobiological correlates of trait anxiety, CD1 mice were selectively bred for extremes in anxiety-related behavior, with high (HAB) and low (LAB) behavior additionally differing behavioral tests reflecting depression-like behavior. Methodology/ principal findings In this study, microarray analysis, situ hybridization, quantitative real-time PCR immunohistochemistry revealed decreased expression the vasopressin gene (Avp) hypothalamic paraventricular (PVN) supraoptic (SON) nuclei adult LAB compared to HAB, NAB (normal behavior) HABxLAB F1 intercross controls, without detecting differences receptor or density. By sequencing regions 2.5 kbp up- downstream Avp locus, we could identify several polymorphic loci, between HAB lines. promoter, a deletion twelve bp Delta(-2180-2191) is particularly likely contribute reduced detected animals under basal conditions. Indeed, allele-specific transcription analysis hypomorphic LAB-specific allele rate by 75% HAB-specific allele, thus explaining line-specific profiles phenotypic features. Accordingly, intra-PVN mRNA levels found correlate behaviors. addition correlative evidence, significant, though moderate, genotype/phenotype association was demonstrated 258 male freely-segregating F2 panel, suggesting causal contribution promoter Discussion Thus, identification polymorphisms explains observed phenotype, further strengthening concept critical involvement centrally released AVP anxiety.