The progress of toxicological Superfund biomedical research during the coming decade will depend upon the mouse as an experimental model to investigate both basic and clinically relevant questions. The mouse is the central experimental model for five of the projects in this Program and all utilize genetically altered mice extensively. The Mouse Molecular Genetics Core provides this Superfund Program's biomedical projects with the most advanced technologies for genetic modification of the mouse genome. Transgenic mice carrying new or novel genes, bacterial artificial chromosomes, or siRNA expression vectors are produced. "Knock-out" mice lacking specific genes of interest or "Knock-in" mice containing a modified version of a gene or gene cluster are created. Mice with human genes substituted for their mouse homologs are developed. Transgenic mice expressing fluorescent markers in specific cells are created. Conditional expression and tissue-specific targeted knock-out strategies are provided. The core provides a wide array of technology- and expertise-intensive services including experimental design consultation, embryonic stem cell homologous recombination, blastocyst microinjection of genetically altered embryonic stem cells into blastocysts to create knock-out or knock-in mice, genetic strategies and consultation, pronuclear injection of transgenes or bacterial artificial chromosomes to create transgenic mice, cryopreservation of mouse lineages, provision of key marker and genetic manipulation strains, and fertility interventions such as in vitro fertilization and ovary transplant. Services are tailored for the projects with special services, ongoing consultation, and high priority. This Core is an outstanding example of how extraordinarily specialized techniques, highly trained, dedicated personnel, and expensive equipment, can be accessed by researchers who could not reasonably expect to develop them on an individual basis. The availability of this Mouse Molecular Genetics Core will enable our biomedical projects to continue to create key novel mouse models and conduct versatile, cutting-edge, molecular genetic research in the mouse with a battery of multidisciplinary state-of-the-art techniques.

Public Health Relevance

The strong conservation in the genomes of humans and mice makes the approach of using transgenic and knock-out mouse technology to create models for human toxicology extremely useful. At the same time, unique differences in metabolism and response to toxic chemicals between mouse and human make the substitution of human genes into the mouse compelling. This Core provides mouse models for our Projects.

Agency
National Institute of Health (NIH)
Institute
National Institute of Environmental Health Sciences (NIEHS)
Type
Hazardous Substances Basic Research Grants Program (NIEHS) (P42)
Project #
2P42ES010337-11A1
Application #
8263115
Study Section
Special Emphasis Panel (ZES1-JAB-J (SF))
Project Start
Project End
Budget Start
2012-04-26
Budget End
2013-03-31
Support Year
11
Fiscal Year
2012
Total Cost
$290,631
Indirect Cost
$102,976
Name
University of California San Diego
Department
Type
DUNS #
804355790
City
La Jolla
State
CA
Country
United States
Zip Code
92093
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