Genetically engineered rodents are essential for understanding gene function in the context of the whole animal. This is especially important for alcohol research as we ultimately seek to understand the role of individual candidate genes on endpoints that can only be studied at the organism level, e.g., alcohol drinking and alcohol-induced behavioral responses. To service the needs of the INIA-West for genetically engineered animals, this core will provide the following services to consortium investigators.
Aim 1 services will provide consultation to investigators regarding model development and construct design.
Aim 2 services all relate to gene targeted mouse production including production of targeting vectors, gene targeting in embryonic stem cells, production of chimerical mice, and breeding to establish mutant mouse lines. Transgenic mouse services are the focus of Aim 3.
This aim i ncludes transgene production, embryo microinjection, and identification of founder animals. Lastly, Aim 4 involves the application of recently developed zinc-finger nuclease technology to produce knockout rats. Zinc-finger nucleases will be purchased from a commercial vendor and this core will inject them into rat embryos and identify the gene targeted rats that result.

Public Health Relevance

The adverse effects of alcohol are a tremendous burden on our medical system and on our society. The use of genetically engineered rodents allows hypotheses regarding ethanol action to be tested at the organismal level.

Agency
National Institute of Health (NIH)
Institute
National Institute on Alcohol Abuse and Alcoholism (NIAAA)
Type
Research Project--Cooperative Agreements (U01)
Project #
5U01AA020889-04
Application #
8718952
Study Section
Special Emphasis Panel (ZAA1)
Program Officer
Reilly, Matthew
Project Start
2011-09-05
Project End
2016-08-31
Budget Start
2014-09-01
Budget End
2015-08-31
Support Year
4
Fiscal Year
2014
Total Cost
Indirect Cost
Name
University of Pittsburgh
Department
Anesthesiology
Type
Schools of Medicine
DUNS #
City
Pittsburgh
State
PA
Country
United States
Zip Code
15213
Rompala, Gregory R; Mounier, Anais; Wolfe, Cody M et al. (2018) Heavy Chronic Intermittent Ethanol Exposure Alters Small Noncoding RNAs in Mouse Sperm and Epididymosomes. Front Genet 9:32
Varodayan, F P; Khom, S; Patel, R R et al. (2018) Role of TLR4 in the Modulation of Central Amygdala GABA Transmission by CRF Following Restraint Stress. Alcohol Alcohol 53:642-649
Rompala, Gregory R; Simons, Alison; Kihle, Brooke et al. (2018) Paternal Preconception Chronic Variable Stress Confers Attenuated Ethanol Drinking Behavior Selectively to Male Offspring in a Pre-Stress Environment Dependent Manner. Front Behav Neurosci 12:257
Pratt, Christopher P; Kuljis, Dika A; Homanics, Gregg E et al. (2017) Tagging of Endogenous BK Channels with a Fluorogen-Activating Peptide Reveals ?4-Mediated Control of Channel Clustering in Cerebellum. Front Cell Neurosci 11:337
Mahnke, Amanda H; Miranda, Rajesh C; Homanics, Gregg E (2017) Epigenetic mediators and consequences of excessive alcohol consumption. Alcohol 60:1-6
Harris, R Adron; Bajo, Michal; Bell, Richard L et al. (2017) Genetic and Pharmacologic Manipulation of TLR4 Has Minimal Impact on Ethanol Consumption in Rodents. J Neurosci 37:1139-1155
Ji, Xincai; Saha, Sucharita; Gao, Guangping et al. (2017) The Sodium Channel ?4 Auxiliary Subunit Selectively Controls Long-Term Depression in Core Nucleus Accumbens Medium Spiny Neurons. Front Cell Neurosci 11:17
Blednov, Yuri A; Borghese, Cecilia M; Ruiz, Carlos I et al. (2017) Mutation of the inhibitory ethanol site in GABAA ?1 receptors promotes tolerance to ethanol-induced motor incoordination. Neuropharmacology 123:201-209
Finegersh, Andrey; Homanics, Gregg E (2016) Chromatin immunoprecipitation and gene expression analysis of neuronal subtypes after fluorescence activated cell sorting. J Neurosci Methods 263:81-8
Ferguson, Carolyn; McKay, Matthew; Harris, R Adron et al. (2013) Toll-like receptor 4 (Tlr4) knockout rats produced by transcriptional activator-like effector nuclease (TALEN)-mediated gene inactivation. Alcohol 47:595-9