Mouse Molecular Genetics Core

Core A: Mouse Molecular Genetics Core

Summary

​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.

Publication

PubMed Central ID: 

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.

PubMedID: 26365380

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.

PubMedID: 26203175

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

PubMedID: 26076042
PubMed Central ID: 

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.

PubMedID: 25915183
PubMed Central ID: 

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.

PubMedID: 25147978
PubMed Central ID: 
Roybal, L. L., Hambarchyan, A., Meadows, J. D., Barakat, N. H., Pepa, P. A., Breen, K. M., Mellon, P. L., Coss, D. (2014)  Roles of binding elements, FOXL2 domains, and interactions with cJUN and SMADs in regulation of FSHβ. Mol Endocrinol. 28(10), 1640-55.

PubMedID: 25105693
PubMed Central ID: 
Hoffmann, H. M., Tamrazian, A., Xie, H., Pérez-Millán, M. I., Kauffman, A. S., Mellon, P. L. (2014) Heterozygous deletion of ventral anterior homeobox (vax1) causes subfertility in mice. Endocrinology. 155(10), 4043-53.
PubMedID: 25060364
PubMed Central ID: 

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.

PubMedID: 25057795
PubMed Central ID: 

Breen, K. M., Mellon, P. L. (2014) Influence of stress-induced intermediates on gonadotropin gene expression in gonadotrope cells. Mol. Cell. Endocrinol. 385(1-2), 71-7.

PubMedID: 24012628
PubMed Central ID: 

Larder, R., Kimura, I., Meadows, J., Clark, D. D., Mayo, S., Mellon, P. L. (2013) Gene dosage of Otx2 is important for fertility in male mice. Mol. Cell. Endocrinol. 377(1-2), 16-22.

PubMedID: 23811236
PubMed Central ID: 

Witham, E. A., Meadows, J. D., Hoffmann, H. M., Shojaei, S., Coss, D., Kauffman, A. S., Mellon, P. L. (2013)  Kisspeptin regulates gonadotropin genes via immediate early gene induction in pituitary gonadotropes. Mol. Endocrinol27(8), 1283-94.

PubMedID: 23770611
PubMed Central ID: 

Glidewell-Kenney, C. A., Shao, P. P., Iyer, A. K., Grove, A. M., Meadows, J. D., Mellon, P. L. (2013) Neurokinin B causes acute GnRH secretion and repression of GnRH transcription in GT1-7 GnRH neurons. Mol. Endocrinol. 27(3), 437-54.

PubMedID: 23393128
PubMed Central ID: 

Clark, D. D., Gorman, M. R., Hatori, M., Meadows, J. D., Panda, S., Mellon, P. L. (2013) Aberrant development of the suprachiasmatic nucleus and circadian rhythms in mice lacking the homeodomain protein Six6. J. Biol. Rhythms. 28(1), 15-25.

PubMedID: 23382588
PubMed Central ID: 

Xie, H., Cherrington, B. D., Meadows, J. D., Witham, E. A., Mellon, P. L. (2013) Msx1 homeodomain protein represses the αGSU and GnRH receptor genes during gonadotrope development. Mol. Endocrinol. 27(3), 422-36.

PubMedID: 23371388
PubMed Central ID: 

Brayman, M. J., Pepa, P. A., Mellon, P. L. (2012) Androgen receptor repression of gonadotropin-releasing hormone gene transcription via enhancer 1. Mol. Cell. Endocrinol. 363(1-2), 92-9.

PubMedID: 22877652
PubMed Central ID: 

Breen, K. M., Thackray, V. G., Hsu, T., Mak-McCully, R. A., Coss, D., Mellon, P. L. (2012) Stress levels of glucocorticoids inhibit LHβ-subunit gene expression in gonadotrope cells. Mol. Endocrinol. 26(10), 1716-31.

PubMedID: 22851703
PubMed Central ID: 

Witham, E. A., Meadows, J. D., Shojaei, S., Kauffman, A. S., Mellon, P. L. (2012) Prenatal exposure to low levels of androgen accelerates female puberty onset and reproductive senescence in mice. Endocrinology. 153(9), 4522-32.

PubMedID: 22778229
PubMed Central ID: 

Ghochani, Y., Saini, J. K., Mellon, P. L., Thackray, V. G. (2012) FOXL2 is involved in the synergy between activin and progestins on the follicle-stimulating hormone β-subunit promoter. Endocrinology. 153(4), 2023-33.

PubMedID: 22294749
PubMed Central ID: 

Brayman, M. J., Pepa, P. A., Berdy, S. E., Mellon, P. L. (2012) Androgen receptor repression of GnRH gene transcription. Mol. Endocrinol. 26(1), 2-13.

PubMedID: 22074952
PubMed Central ID: 

Yueh, M. F., Mellon, P. L., Tukey, R. H. (2011) Inhibition of human UGT2B7 gene expression in transgenic mice by the constitutive androstane receptor. Mol Pharmacol. 79(6),1053-60.

PubMedID: 21415305
PubMed Central ID: 

Larder, R., Clark, D. D., Miller, N. L., Mellon, P. L. (2011) Hypothalamic dysregulation and infertility in mice lacking the homeodomain protein Six6. J. Neurosci. 31(2), 426-38.

PubMedID: 21228153
PubMed Central ID: 

Miller, N. L., Wevrick, R., Mellon, P. L. (2009)  Necdin, a Prader-Willi syndrome candidate gene, regulates gonadotropin-releasing hormone neurons during development. Hum. Mol. Genet. 18(2), 248-60.

PubMedID: 18930956
PubMed Central ID: 

Cherrington, B. D., Bailey, J. S., Diaz, A. L., Mellon, P. L. (2008) NeuroD1 and Mash1 temporally regulate GnRH receptor gene expression in immortalized mouse gonadotrope cells. Mol Cell Endocrinol. 295(1-2),106-14.

PubMedID: 18760324

Main Contact Information

Core Leader

  • Dr. Pamela L. Mellon

Superfund Related Core Members:

  • Ella Kothari
  • Jason Meadows
  • Mary Sunshine
  • Jun Zhao

Other Superfund Projects:

Training Core

 

Resources (Mellon)

UCSD Biomedical Sciences Graduate Program

UCSD Department of Reproductive Medicine

UCSD School of Medicine, Department of Neurosciences

Mellon Laboratory

References From PubMed (NCBI)

Pamela L. Mellon, Ph.D., Core Leader
University of California, San Diego
Department of Reproductive Medicine, Mailcode 0674
9500 Gilman Drive
La Jolla, CA 92093-0674
P: 858-534-1312 F: 858-534-1438
E-mail: pmellon@ucsd.edu

Contact

UCSD Superfund Research Center
University of California, San Diego
Pharmacology Department
9500 Gilman Drive, Mail Code 0722
La Jolla, CA 92093-0722