This proposal aims to characterize the effects of a variable genetic element in regulation of expression of the vole vasopressin 1a receptor (V1aR) gene. Vasopressin and the V1aR are involved in the regulation of species-specific social behaviors. Receptor distribution patterns are species-specific and correlate with social structure. Monogamous and non-monogamous voles differ in their behavioral response to vasopressin and expression pattern of V1aR in the brain. In addition, there is a tremendous amount of intra-specific variability in V1aR expression in monogamous prairie voles. A large, highly repetitive microsatellite region is found in the 5' flanking region of the VlaR gene of monogamous voles but not in non-monogamous vole species. Within prairie vole, the length of this microsatellite correlates with the level of VlaR binding in the brain. This research proposal will test the hypothesis that i) this polymorphic promoter sequence plays a role in the expression of the VlaR gene, and that ii) the individual variability in V1aR expression resulting from this variable promoter structure translates into individual variability in social behavior. Luciferase reporter assays in cell culture and a selective prairie vole breeding strategy with extensive behavioral characterization and subsequent molecular analysis will be used to test these hypotheses. This research will provide a possible molecular mechanism producing intra-specific variability in gene expression and behavior, which may be relevant to psychopathologies. ? ?
| Fondon 3rd, John W; Hammock, Elizabeth A D; Hannan, Anthony J et al. (2008) Simple sequence repeats: genetic modulators of brain function and behavior. Trends Neurosci 31:328-34 |
| Hammock, Elizabeth A D (2007) Gene regulation as a modulator of social preference in voles. Adv Genet 59:107-27 |
| Hammock, E A D; Lim, M M; Nair, H P et al. (2005) Association of vasopressin 1a receptor levels with a regulatory microsatellite and behavior. Genes Brain Behav 4:289-301 |
| Hammock, Elizabeth A D; Young, Larry J (2005) Microsatellite instability generates diversity in brain and sociobehavioral traits. Science 308:1630-4 |
| Young, Larry J; Murphy Young, Anne Z; Hammock, Elizabeth A D (2005) Anatomy and neurochemistry of the pair bond. J Comp Neurol 493:51-7 |
| Hammock, Elizabeth A D; Young, Larry J (2004) Functional microsatellite polymorphism associated with divergent social structure in vole species. Mol Biol Evol 21:1057-63 |
| Lim, M M; Hammock, E A D; Young, L J (2004) The role of vasopressin in the genetic and neural regulation of monogamy. J Neuroendocrinol 16:325-32 |
