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.
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.
|Patel, Niraj S; Doycheva, Iliana; Peterson, Michael R et al. (2015) Effect of weight loss on magnetic resonance imaging estimation of liver fat and volume in patients with nonalcoholic steatohepatitis. Clin Gastroenterol Hepatol 13:561-568.e1|
|Seki, Ekihiro; Schwabe, Robert F (2015) Hepatic inflammation and fibrosis: functional links and key pathways. Hepatology 61:1066-79|
|Fan, Weiwei; Evans, Ronald (2015) PPARs and ERRs: molecular mediators of mitochondrial metabolism. Curr Opin Cell Biol 33:49-54|
|Yang, Ling; Roh, Yoon Seok; Song, Jingyi et al. (2014) Transforming growth factor beta signaling in hepatocytes participates in steatohepatitis through regulation of cell death and lipid metabolism in mice. Hepatology 59:483-95|
|Kunz, Hans-Henning; Gierth, Markus; Herdean, Andrei et al. (2014) Plastidial transporters KEA1, -2, and -3 are essential for chloroplast osmoregulation, integrity, and pH regulation in Arabidopsis. Proc Natl Acad Sci U S A 111:7480-5|
|Schnabl, Bernd; Brenner, David A (2014) Interactions between the intestinal microbiome and liver diseases. Gastroenterology 146:1513-24|
|Maruo, Yoshihiro; Morioka, Yoriko; Fujito, Hiroshi et al. (2014) Bilirubin uridine diphosphate-glucuronosyltransferase variation is a genetic basis of breast milk jaundice. J Pediatr 165:36-41.e1|
|Dowding, J M; Song, W; Bossy, K et al. (2014) Cerium oxide nanoparticles protect against A?-induced mitochondrial fragmentation and neuronal cell death. Cell Death Differ 21:1622-32|
|Roybal, Lacey L; Hambarchyan, Arpi; Meadows, Jason D et al. (2014) Roles of binding elements, FOXL2 domains, and interactions with cJUN and SMADs in regulation of FSH?. Mol Endocrinol 28:1640-55|
|Nakagawa, Hayato; Umemura, Atsushi; Taniguchi, Koji et al. (2014) ER stress cooperates with hypernutrition to trigger TNF-dependent spontaneous HCC development. Cancer Cell 26:331-43|
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