We propose to develop genomic resources for the prairie vole (Microtus ochrogaster) that will significantly enhance the value of this species as a model for understanding the genetic and neurobiological mechanisms governing social behavior. Microtine rodents are ideally suited for investigating the mechanisms underlying variation in social behavior. The monogamous prairie voles (M. ochrogaster) are highly affiliative, form life-long social attachments and display high levels of biparental care. In contrast, montane (M. montanus) and meadow voles (M. pennsylvanicus) are relatively asocial, do not form social attachments, and are minimally parental. In addition to this species diversity, there is remarkable intra-species variation in social behavior among prairie voles, both within a population and among populations of different geographical ranges. This behavioral diversity provides and exciting opportunity to discover novel genes contributing to the regulation and diversity of social behavior. Over the past 15 years, there has been remarkable progress in understanding the neural and molecular mechanisms regulating social bonding and parental care in prairie voles. These studies have focused on a few candidate neuropeptides and neurotransmitter systems (e.g. oxytocin, vasopressin, CRF, dopamine and their respective receptors). The discoveries made in prairie voles have important implications for psychiatric disorders associated with impairments in social behavior, including autism, schizophrenia and depression. In fact, principles discovered thus far using the prairie vole model have already been applied to autism research with promising results. However, the development of this model to its full potential is limited by the paucity of molecular and genomic resources available for the prairie vole. We propose to generate two genomic resources that will greatly accelerate investigations of the basic genetic mechanisms regulating social behavior. First, we will construct a microsatellite-based genetic linkage map of the prairie vole genome that can be used in Quantitative Trait Locus (QTL) studies. We will also construct a 10X coverage BAC library of the prairie vole genome. We will use this resource to isolate clones containing several genes of interest to the prairie vole research community. Used together, these resources will facilitate the discovery of novel genes involved in the regulation of social behavior. These resources will be made freely available to the rapidly growing prairie vole research community.
Psychiatric disorders such as autism spectrum disorder, schizophrenia, and depression are associated with severe impairments in the social domain. Understanding the neurobiological and genetic mechanisms underlying the regulation of normal social behavior will provide insights into the systems that may be disrupted in these devastating disorders. The resources developed through this proposal will accelerate the discovery of novel genes contributing to variation in social behavior, potentially leading to novel therapeutic targets for treating these disorders. ? ?
| McGraw, Lisa A; Davis, Jamie K; Thomas, Pamela J et al. (2012) BAC-based sequencing of behaviorally-relevant genes in the prairie vole. PLoS One 7:e29345 |
| McGraw, Lisa A; Davis, Jamie K; Young, Larry J et al. (2011) A genetic linkage map and comparative mapping of the prairie vole (Microtus ochrogaster) genome. BMC Genet 12:60 |
| McGraw, Lisa A; Young, Larry J (2010) The prairie vole: an emerging model organism for understanding the social brain. Trends Neurosci 33:103-9 |
| McGraw, Lisa A; Davis, Jamie K; Lowman, Josh J et al. (2010) Development of genomic resources for the prairie vole (Microtus ochrogaster): construction of a BAC library and vole-mouse comparative cytogenetic map. BMC Genomics 11:70 |
