Core A: Mouse Molecular Genetics Core
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.
Hoffmann, H. M., Trang, C., Gong, P., Kimura, I., Pandolfi, E. C., and Mellon, P. L. (2016) Deletion of Vax1 from GnRH Neurons Abolishes GnRH Expression and Leads to Hypogonadism and Infertility. Journal of Neuroscience. 36: 3506-3518. doi: 10.1523/JNEUROSCI.2723-15.2016.
Skowronska-Krawczyk, D., Zhao, L., Zhu, J., Weinreb, R. N., Cao, G., Luo, J., Flagg, K., Patel, S., Wen, C., Krupa, M., Luo, H., Ouyang, H., Lin, D., Wang, W., Li, G., Xu, Y., Li, O., Chung, C., Yeh, E., Jafari, M., Ai, M., Zhong, Z., Shi, W., Zheng, L., Krawczyk, M., Chen, D., Shi, C., Zin, C., Zhu, J., Mellon, P. L., Gao, W., Abagyan, R., Zhang, L., Sun, X., Zhong, S., Zhuo, Y., Rosenfeld, M. G., Liu, Y., Zhang, K. (2015) P16INK4a Upregulation Mediated by SIX6 Defines Retinal Ganglion Cell Pathogenesis in Glaucoma. Cell Mol. 59(6), 931-40. doi: 10.1016/j.molcel.2015.07.027.
Kauffman, A. S., Thackray, V. G., Ryan, G. E., Tolson, K. P., Glidewell-Kenney, C. A., Semaan, S. J., Poling, M. C., Iwata, N., Breen, K. M., Duleba, A. J., Stener-Victorin, E., Shimasaki, S., Webster, N. J., Mellon, P. L. (2015) A Novel Letrozole Model Recapitulates Both the Reproductive and Metabolic Phenotypes of Polycystic Ovary Syndrome in Female Mice. Biol Reprod. pii: biolreprod.115.131631.
Stephens, S. B., Tolson, K. P., Rouse, M. L., Poling, M. C., Hashimoto-Partyka, M. K., Mellon, P. L., Kauffman, A. S. (2015) Absent Progesterone Signaling in Kisspeptin Neurons Disrupts the LH Surge and Impairs Fertility in Female Mice. Endocrinology. en20151300
Xie, H., Hoffmann, H. M., Meadows, J. D., Mayo, S. L., Trang, C., Leming, S. S., Maruggi, C., Davis, S. W., Larder, R., Mellon, P. L. (2015) Homeodomain Proteins SIX3 and SIX6 Regulate Gonadotrope-specific Genes During Pituitary Development. Mol Endocrinol. 29(6), 842-55.
Ahow, M., Min, L., Pampillo, M., Nash, C., Wen, J., Soltis, K., Carroll, R. S., Glidewell-Kenney, C. A., Mellon, P. L., Bhattacharya, M., Tobet, S. A., Kaiser, U. B., Babwah, A.V. (2014) KISS1R Signals Independently of Gαq/11 and Triggers LH Secretion via the β-Arrestin Pathway in the Male Mouse. Endocrinology. 155(11), 4433-46.
Glidewell-Kenney, C. A., Trang, C., Shao, P. P., Gutierrez-Reed, N., Uzo-Okereke, A. M., Coss, D., Mellon, P. L. (2014) Neurokinin B induces c-fos transcription via protein kinase C and activation of serum response factor and Elk-1 in immortalized GnRH neurons. Endocrinology. 155(10), 3909-19.
Main Contact Information
- Dr. Pamela L. Mellon
Superfund Related Core Members:
- Ella Kothari
- Jason Meadows
- Mary Sunshine
- Jun Zhao
Other Superfund Projects:
UCSD Superfund Research Center
University of California, San Diego
9500 Gilman Drive, Mail Code 0722
La Jolla, CA 92093-0722