Portland Genetic Animal Models Core

DESCRIPTION (provided by applicant):
Due to the differences among the genetic animals models being maintained, used
and developed in 5 of the 6 INIA sites, a separate U-24 application to support
genetic animal models is being submitted from each site. Dr. John Crabbe,
Professor of Behavioral Neuroscience, Oregon Health Sciences University
(OHSU), will serve as coordinator of the overall Genetic Animal Models Core
described in this application. The major goal of the GAMC is to integrate
animal model development, availability and usage across sites. Genetic animal
models have been a major staple of alcohol research since the first were
developed in the late 1940?s. It has oeen known for many years that animals
experienced with alcohol self-administration and/or dependent on alcohol will
increase their intake for a relatively short period of time after a period of
withdrawal. However, these and other existing models are not yet optimal.
Generally, the magnitude and architecture of the response does not
convincingly display either gross excess or obvious loss of control that
extends for a long time after the initial period of intoxicating
self-administration. Virtually nothing is known about the genetic
redisposition to self-administration potentiated by any of the above
manipulations. Little to nothing has been done to characterize any of these
phenomena in existing mouse genetic models of high or low ethanol drinking or
high or low withdrawal. The general goals of the GAMC are to facilitate the
development of more robust phenotypes and genotypes; facilitate the
exploration of gene X environment interactions and facilitate development of
novel genetic technology to explore the two-hit hypothesis, i.e. that at least
two clusters of genes must be dysregulated to produce abusive
self-administration; to achieve coordinated genetic animal model utilization
and development across INIA sites and Cores; and to provide relevant data to
the informatics Core. At the Portland site, specific emphasis is placed on
development of novel models, coordination of animals and data, and provision
of resources for rendering animals physically dependent on ethanol.