We maintain a large number of unique genotypes of mice for alcohol research studies. These animals are used in research supported by multiple R01s, U01s, the Portland Alcohol Research Center (PARC) P60 grant, and several VA Merit Review Grants. These animals have been used for research by investigators in Portland, Oregon and at many other sites around the world. Partial support for all these genotypes is budgeted within the primary grants employing them, but cost inflation and the lack of synchrony between grant cycles and actual use has led us to fall further and further behind our ability to support these mice. Our ability to keep up is due partly to inflation exceeding the NIH COLA limits, and partly to budget caps on several of the principal supporting grants (P60, UOIs, and VA Merit Reviews). The proposed R24 seeks modest support to maintain these genotypes, in each case cost-shared with user fees and maintenance support from the parent grants. There are four aims:
Aim 1. Help maintain core breeding colonies of long- term selected lines and their genetically heterogeneous control lines (WSP-1, WSP-2, WSR-1, WSR-2, FAST-1, FAST-2, SLOW-1, SLOW-2, WSC, HDID-1, HDID-2, and HS/Npt).
Aim 2. Help maintain core breeding colonies of congenic strains and lines, and their progenitor inbred strains, for quantitative trait locus (QTL) gene mapping studies (17 genotypes covering parts of chromosomes 1, 6, and 19 and their progenitor inbred strains, C57BL/6J (86) and DBA /2J (D2), and two genotypes covering QTLs on chromosomes 1 and 11, iWSP2, iWSR-1).
Aim 3. Help maintain core breeding colonies for the genetically heterogeneous stock HS-CC, derived by the Complex Trait Consortium for advanced intercross QTL mapping studies.
Aim 4. Partially defray costs for cryopreservation of long term selected lines and congenic strains. Cryopreservation protects against catastrophic loss of crucial genotypes as well as providing access for potential future use [HOT-1, HOT-2, COLD-1, COLD-2, WSP-1, WSP-2, WSR-1, WSR-2, HDID-1, HDID-2, and 22 congenic strains (5 to be cryopreserved) for quantitative trait loci on chromosomes 1,4, 11 and 19]. All genotypes covered are freely available to interested investigators at cost. Funds to support distribution are not requested, as this support is provided under the primary grants supporting the various genotypes. Funds to support breeding and testing of additional animals are also not requested here, but rather under the parent grants.

Public Health Relevance

Genetic animal models, particularly with mice and rats, have been major contributors to our understanding of the pathophysiology of alcohol use disorders. The genetics and genomics resources available for mouse makes this species especially valuable for ascertaining genetic risk and developing novel pharmacotherapies. The models for which we seek support are unique.

Agency
National Institute of Health (NIH)
Institute
National Institute on Alcohol Abuse and Alcoholism (NIAAA)
Type
Resource-Related Research Projects (R24)
Project #
5R24AA020245-03
Application #
8451998
Study Section
Special Emphasis Panel (ZAA1-GG (01))
Program Officer
Reilly, Matthew
Project Start
2011-04-05
Project End
2016-03-31
Budget Start
2013-04-01
Budget End
2014-03-31
Support Year
3
Fiscal Year
2013
Total Cost
$200,436
Indirect Cost
$41,360
Name
Oregon Health and Science University
Department
Other Basic Sciences
Type
Schools of Medicine
DUNS #
096997515
City
Portland
State
OR
Country
United States
Zip Code
97239
Crabbe, John C; Schlumbohm, Jason P; Hack, Wyatt et al. (2016) Fear conditioning in mouse lines genetically selected for binge-like ethanol drinking. Alcohol 52:25-32
Tipps, Megan E; Raybuck, Jonathan D; Kozell, Laura B et al. (2016) G Protein-Gated Inwardly Rectifying Potassium Channel Subunit 3 Knock-Out Mice Show Enhanced Ethanol Reward. Alcohol Clin Exp Res 40:857-64
Greenberg, G D; Huang, L C; Spence, S E et al. (2016) Nest building is a novel method for indexing severity of alcohol withdrawal in mice. Behav Brain Res 302:182-90
Hashimoto, Joel G; Wiren, Kristine M; Wilhelm, Clare J (2016) A neurotoxic alcohol exposure paradigm does not induce hepatic encephalopathy. Neurotoxicol Teratol 56:35-40
Crabbe, John C (2016) Progress With Nonhuman Animal Models of Addiction. J Stud Alcohol Drugs 77:696-9
Greenberg, Gian D; Phillips, Tamara J; Crabbe, John C (2016) Effects of acute alcohol withdrawal on nest building in mice selectively bred for alcohol withdrawal severity. Physiol Behav 165:257-66
Phillips, T J; Mootz, J R K; Reed, C (2016) Identification of Treatment Targets in a Genetic Mouse Model of Voluntary Methamphetamine Drinking. Int Rev Neurobiol 126:39-85
Shabani, Shkelzen; Houlton, Sydney K; Hellmuth, Laura et al. (2016) A Mouse Model for Binge-Level Methamphetamine Use. Front Neurosci 10:493
Phillips, T J; Reed, C; Pastor, R (2015) Preclinical evidence implicating corticotropin-releasing factor signaling in ethanol consumption and neuroadaptation. Genes Brain Behav 14:98-135
Wilhelm, Clare J; Hashimoto, Joel G; Roberts, Melissa L et al. (2015) Females uniquely vulnerable to alcohol-induced neurotoxicity show altered glucocorticoid signaling. Brain Res 1601:102-16

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