It is clear that the progress of toxicological Superfund research during the coming decade will depend upon the mouse as an experimental model to investigate both basic and clinically relevant questions. The high degree of conservation in the genomes of humans and mice makes the approach of using transgene and knock-out gene technology to create models for human toxicology extremely attractive. 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 this Superfund projects with the most advanced technologies for genetic modification of the mouse genome. Transgenic mice carrying new or novel genes and 'Knock-out' or 'Knock-in' mice lacking specific genes of interest or containing modified version of key genes are created. Conditional expression and Cre/LoxP 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, Cre transfection of embryonic stem cells for LoxP excision, blastocyst microinjection of genetically altered embryonic stem cells into blastocysts to create knock-out or knock-in mice, pronuclear injection of transgenes or bacterial artificial chromosomes to create transgenic mice, embryo injecion of Lentivirus vectors, cryopreservation of embryos, and fertility interventions such as in vitro fertilization and ovary transplant. Services are tailored for the projects with special service 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 Transgenic and Knock-out Mouse Core will enable the projects to conduct versatile, cutting-edge, molecular genetic research in the mouse with a battery of multidisciplinary state-of-the-art techniques.

Agency
National Institute of Health (NIH)
Institute
National Institute of Environmental Health Sciences (NIEHS)
Type
Hazardous Substances Basic Research Grants Program (NIEHS) (P42)
Project #
5P42ES010337-08
Application #
7425864
Study Section
Special Emphasis Panel (ZES1)
Project Start
Project End
Budget Start
2007-04-01
Budget End
2008-03-31
Support Year
8
Fiscal Year
2007
Total Cost
$285,324
Indirect Cost
Name
University of California San Diego
Department
Type
DUNS #
804355790
City
La Jolla
State
CA
Country
United States
Zip Code
92093
Brouha, Sharon S; Nguyen, Phirum; Bettencourt, Ricki et al. (2018) Increased severity of liver fat content and liver fibrosis in non-alcoholic fatty liver disease correlate with epicardial fat volume in type 2 diabetes: A prospective study. Eur Radiol 28:1345-1355
Hsu, Po-Kai; Takahashi, Yohei; Munemasa, Shintaro et al. (2018) Abscisic acid-independent stomatal CO2 signal transduction pathway and convergence of CO2 and ABA signaling downstream of OST1 kinase. Proc Natl Acad Sci U S A 115:E9971-E9980
Dhar, Debanjan; Antonucci, Laura; Nakagawa, Hayato et al. (2018) Liver Cancer Initiation Requires p53 Inhibition by CD44-Enhanced Growth Factor Signaling. Cancer Cell 33:1061-1077.e6
Febbraio, Mark A; Reibe, Saskia; Shalapour, Shabnam et al. (2018) Preclinical Models for Studying NASH-Driven HCC: How Useful Are They? Cell Metab :
Fujiwara, Ryoichi; Yoda, Emiko; Tukey, Robert H (2018) Species differences in drug glucuronidation: Humanized UDP-glucuronosyltransferase 1 mice and their application for predicting drug glucuronidation and drug-induced toxicity in humans. Drug Metab Pharmacokinet 33:9-16
Hartmann, Phillipp; Hochrath, Katrin; Horvath, Angela et al. (2018) Modulation of the intestinal bile acid/farnesoid X receptor/fibroblast growth factor 15 axis improves alcoholic liver disease in mice. Hepatology 67:2150-2166
Ganguly, Abantika; Guo, Lan; Sun, Lingling et al. (2018) Tdp1 processes chromate-induced single-strand DNA breaks that collapse replication forks. PLoS Genet 14:e1007595
Tripathi, Anupriya; Debelius, Justine; Brenner, David A et al. (2018) The gut-liver axis and the intersection with the microbiome. Nat Rev Gastroenterol Hepatol 15:397-411
Chen, Shujuan; Tukey, Robert H (2018) Humanized UGT1 Mice, Regulation of UGT1A1, and the Role of the Intestinal Tract in Neonatal Hyperbilirubinemia and Breast Milk-Induced Jaundice. Drug Metab Dispos 46:1745-1755
Desai, Archita P; Mohan, Prashanthinie; Roubal, Anne M et al. (2018) Geographic Variability in Liver Disease-Related Mortality Rates in the United States. Am J Med 131:728-734

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