Animal & Resource Core - C001
Core Lead: Cheryl Reed Williams
The incorporation of an Animal & Resource & Resource Core in the PARC reflects the needs of our research center and its synergistic focus on: 1) shared animal models and enhanced translatability between monkey and mouse investigations, 2) implementation of standard operating procedures (SOPs) to enhance replicability across projects, 3) coalescence around the Center Theme: The Role of the Tetrapartite Synapse in Risk for and Response to Alcohol Drinking, 4) mechanism and treatment target validation in the study of impacts on alcohol drinking, and 5) provision of streamlined services between PARC investigators and the Integrated Genomics Laboratory (IGL), which provides information about (1) gene expression differences related to risk for alcohol drinking and (2) the effects of alcohol drinking on the expression of specific genes.
To promote these center-wide initiatives, the Animal & Resource Core performs several roles and services:
1. Establish, maintain and distribute genetic mouse models.
2. Conduct SOPs for behavioral mouse phenotypes under study by research projects.
3. Provide next-generation sequencing services for all research projects.
Mouse Genetic Models
Researchers of the PARC have utilized many genetic animal models in their work over the years of the Center’s existence. The mouse genetic models listed below were developed locally and are now available to the research community. This information can also be found here: Selectively Bred Lines and Inbred Strains Created from Selectively Bred Lines.
If you are interested in obtaining one of our currently available mouse models, please contact Center Administrator, Josh Merrick at merrick@ohsu.edu or the NIH Mutant mouse Resource & Research Centers (MMRRC) for models preserved there (see Table below; email: service@mmrrc.org)
Selectively Bred Lines and Inbred Strains Created from Selectively Bred Lines
| Line Designation | Description | Developing PI |
|---|---|---|
| FAST-1, FAST-2, SLOW-1, SLOW-2 | FAST replicate 1&2 and SLOW replicate 1&2. Lines were bred to display heightened (FAST) or reduced (SLOW) sensitivity to the locomotor activating effects of a single 2.0 g/kg IP injection of alcohol (ethanol), compared to response after saline injection; all are embryo cryopreserved and available from the MMRRC, email: service@mmrrc.org | Tamara Phillips |
| WSP-1, WSP-2, WSR-1, WSR-2 | Withdrawal Seizure-Prone replicate 1&2 and Withdrawal Seizure-Resistant replicate 1&2. Lines were bred to display severe (WSP) or mild (WSR) handling-induced convulsions after withdrawal from chronic ethanol vapor inhalation; all are embryo cryopreserved and available from the MMRRC, email: service@mmrrc.org | John Crabbe |
| WSC-1, WSC-2 | Withdrawal Seizure Control replicate 1&2. Randomly bred controls bred in parallel with WSP and WSR selected lines; all are embryo cryopreserved and available from the MMRRC, email: service@mmrrc.org | John Crabbe |
| IWSP-1, IWSP-2, IWSR-1, IWSR-2 | Inbred strains derived from WSP & WSR selectively bred lines, beginning with generation S26G33-52. Fully inbred. All are embryo cryopreserved and available from The Jackson Laboratory. | John Crabbe |
| HOT-1, HOT-2, COLD-1, COLD-2 | HOT & COLD mouse lines were selectively bred for extreme (COLD) or mild (HOT) hypothermia 30-60 minutes after 3 g/kg ethanol. All are embryo cryopreserved and available from The Jackson Laboratory. | John Crabbe |
| HDID-1, HDID-2 | The HDID replicate mouse lines are being actively selectively bred for high blood ethanol concentration (BEC) after consumption of ethanol (20%) in a limited access period of 4 hours called, "Drinking in the Dark (DID)." Embryos are cryopreserved and available from the MMRRC, email: service@mmrrc.org. | John Crabbe/Angela Ozburn |
| iHDID-1, iHDID-2 | Inbred strains derived from the HDID selectively bred lines. The iHDID-1 mice are fully inbred; inbreeding began from S26 mice. The iHDID-2 mice are partially inbred using the highest BEC individuals; inbreeding began from S37 mice. As of January 2022 iHDID-2 are 2 generations away from full inbreeding. Live mice are available for iHDID-1 and iHDID-2 strain and both strains are cryopreserved and available from the MMRRC, email: service@mmrrc.org. | John Crabbe/Angela Ozburn |
| HAFT-1, LAFT-1 | The High Acute Functional Tolerance (HAFT) and Low Acute Functional Tolerance (LAFT) replicate 1 mouse lines were selectively bred by Drs. Erwin & Deitrich (UCHSC, Denver, CO) to display high (HAFT) or low (LAFT) acute functional tolerance to ethanol, calculated as the difference in blood ethanol concentrations at the time of regaining the ability to stay for 1 minute on a stationary dowel (12.7mm) after two consecutive injections of ethanol (1.75 g/kg followed by 2.0 g/kg, IP). Embryos are cryopreserved and available from the MMRRC, email: service@mmrrc.org | John Crabbe |
| HP-2/LP-2 | The second replicate of the high (HP) and low (LP) preference lines were selectively bred for high or low preference for 10% v/v ethanol offered vs. water. Methods used for the creation of this second replicate were identical to those described in Colville et al. (2017, Genes Brain Behavior 16(4) 462-471, doi/10.1111/gbb.12367). These animals are available upon request, email: Tamara Phillips at phillipt@ohsu.edu | Tamara Phillips/Robert Hitzemann |
FAST/SLOW, WSP/WSR, HOT/COLD, and HAFT/LAFT selections were bred bi-directionally (high vs low) over 15 or more generations for the trait indicated from the founder populations of the HS/Ibg 8-way inbred strain cross (formerly available from the Institute of Behavior Genetics, Boulder, CO). Independently- derived replicated lines were developed for all four selections. The HAFT/LAFT selection was created by Dr. V. G. Erwin (UCHSC, Denver, CO) and breeding stock of the first replicate were provided to Dr. Crabbe in 2006. Embryos are cryopreserved and available from the MMRRC.
HDID-1 and -2 were bred uni-directionally (high lines only) for the trait indicated from founder populations of the HS/Npt 8-way inbred strain cross (previously available from Dr. R. Hitzemann, OHSU, Portland, OR but now extinct). Embryos are cryopreserved and available from the MMRRC.
Short Term Selectively Bred (STSB) lines are periodically developed for various behavioral traits by PARC Researchers for use in gene mapping, microarray, and genomic-related studies. STSB lines for high and low ethanol preference (HP and LP, respectively) have been the focus of PARC research during the past decade. The current replicate (second replicate) HP and LP mice are available upon request. The HP and LP mice were selected from founder population of HS-CC mice (formerly available from Dr. R. Hitzemann, OHSU, Portland, OR, but now extinct). The first replicate of these lines is discussed in Colville et al., 2017 (Genes Brain Behavior 16(4): 462-471), and the second replicate was completed in April 2021 using identical method.