Transgenic Core Facility


Transgenic Core Facillity graphic

Facility staff:

Christie Nagy, John Raucci, George Heath, Taylor Walker, MaryAnn DeMaria

Research Interests

Since the inception of the Department of Genetics at St. Jude in the Summer of 1993, its staff have worked together to create a core facility that would produce transgenic and knockout mice for the researchers at St. Jude. The facility became operational as a core resource in early 1995 and has since produced a large number of knockout and transgenic mouse strains. Currently, 3 full-time research technologists perform all manipulations necessary for the generation of genetically engineered mice. As a standard practice, researchers prepare injection-ready DNA or targeted ES cells and the core facility gives them the genetically modified mice.

The instant success of this facility has greatly expanded the scope of research opportunities at St. Jude, and many investigators now use mouse models to study gene function in vivo. The Transgenic Core Facility has produced mice for researchers in Biochemistry, Developmental Neurobiology, Experimental Hematology, Experimental Oncology, Genetics, Pathology and Laboratory Medicine, Tumor Cell Biology, and Virology and Molecular Biology. These efforts have produced exciting results in the areas of hematopoiesis, leukemia, lymphocyte development, lysosomal storage disorders, nucleocytoplasmic trafficking, neurodegenerative diseases, signal transduction, and tumorigenesis.

Selected publications describing the use of genetically modified mice generated at St. Jude:

Abner CW, McKinnon PJ. The DNA double-strand break response in the nervous system. DNA Repair (Amst) 3:1141-7, 2004.

Schuendeln MM, Piekorz RP, Wichmann C, Lee Y, McKinnon PJ, Boyd K, Takahashi Y, Ihle JN. The centrosomal, putative tumor suppressor protein TACC2 is dispensable for normal development, and deficiency does not lead to cancer. Mol Cell Biol 24:6403-9, 2004.

Kitagawa R, Bakkenist CJ, McKinnon PJ, Kastan MB. Phosphorylation of SMC1 is a critical downstream event in the ATM-NBS1-BRCA1 pathway. Genes Dev 8:1423-38, 2004. Epub 2004 Jun 02.

Hauser EC, Kasperzyk JL, d'Azzo A, Seyfried TN. Inheritance of lysosomal acid beta-galactosidase activity and gangliosides in crosses of DBA/2J and knockout mice. Biochem Genet 42:241-57, 2004.

Tessitore A, del P Martin M, Sano R, Ma Y, Mann L, Ingrassia A, Laywell ED, Steindler DA, Hendershot LM, d'Azzo A. GM1-ganglioside-mediated activation of the unfolded protein response causes neuronal death in a neurodegenerative gangliosidosis. Mol Cell 15:753-66, 2004.

Kasperzyk JL, El-Abbadi MM, Hauser EC, D'Azzo A, Platt FM, Seyfried TN. N-butyldeoxygalactonojirimycin reduces neonatal brain ganglioside content in a mouse model of GM1 gangliosidosis. J Neurochem 89:645-53, 2004.

Bonten EJ, Wang D, Toy JN, Mann L, Mignardot A, Yogalingam G, D'Azzo A. Targeting macrophages with baculovirus-produced lysosomal enzymes: implications for enzyme replacement therapy of the glycoprotein storage disorder galactosialidosis. FASEB J 18:971-3, 2004. Epub 2004 Apr 14.

Nastasi T, Bongiovanni A, Campos Y, Mann L, Toy JN, Bostrom J, Rottier R, Hahn C, Conaway JW, Harris AJ, D'Azzo A. Ozz-E3, a muscle-specific ubiquitin ligase, regulates beta-catenin degradation during myogenesis. Dev Cell 6:269-82, 2004.

Korah N, Smith CE, D'Azzo A, Mui J, Hermo L. Characterization of cell- and region-specific abnormalities in the epididymis of cathepsin A deficient mice. Mol Reprod Dev 6:358-73, 2003.

Schacht V, Ramirez MI, Hong YK, Hirakawa S, Feng D, Harvey N, Williams M, Dvorak AM, Dvorak HF, Oliver G, Detmar M. T1alpha/podoplanin deficiency disrupts normal lymphatic vasculature formation and causes lymphedema. EMBO J 15:3546-56, 2003.

Prado CL, Pugh-Bernard AE, Elghazi L, Sosa-Pineda B, Sussel L. Ghrelin cells replace insulin-producing beta cells in two mouse models of pancreas development. Proc Natl Acad Sci USA 101:2924-9, 2004.

Wang J, Elghazi L, Parker SE, Kizilocak H, Asano M, Sussel L, Sosa-Pineda B. The concerted activities of Pax4 and Nkx2.2 are essential to initiate pancreatic beta-cell differentiation. Dev Biol 266:178-89, 2004.

Selleri L, DiMartino J, van Deursen J, Brendolan A, Sanyal M, Boon E, Capellini T, Smith KS, Rhee J, Popperl H, Grosveld G, Cleary ML. The TALE homeodomain protein Pbx2 is not essential for development and long-term survival. Mol Cell Biol 24:5324-31, 2004.

Donovan SL, Dyer MA. Developmental defects in Rb-deficient retinae. Vision Res 44:3323-3333, 2004.

Zhang J, Schweers B, Dyer MA. The first knockout mouse model of retinoblastoma. Cell Cycle 3:952-9, 2004.

Zhang J, Gray J, Wu L, Leone G, Rowan S, Cepko CL, Zhu X, Craft CM, Dyer MA. Rb regulates proliferation and rod photoreceptor development in the mouse retina. Nat Genet 36:351-60, 2004.

Romer JT, Kimura H, Magdaleno S, Sasai K, Fuller C, Baines H, Connelly M, Stewart CF, Gould S, Rubin LL, Curran T. Suppression of the Shh pathway using a small molecule inhibitor eliminates medulloblastoma in Ptc1(+/-)p53(-/-) mice. Cancer Cell 6:229-40, 2004

Chattopadhyay S, Kingsley E, Serour A, Curran TM, Brooks AI, Pearce DA. Altered gene expression in the eye of a mouse model for batten disease. Invest Ophthalmol Vis Sci 45:2893-905, 2004.

Romer JT, Curran T. Medulloblastoma and retinoblastoma: oncology recapitulates ontogeny. Cell Cycle 3:917-9, 2004.

Fraser MM, Zhu X, Kwon CH, Uhlmann EJ, Gutmann DH, Baker SJ. Pten loss causes hypertrophy and increased proliferation of astrocytes in vivo. Cancer Res 2004 64:7773-9, 2004.

Kwon CH, Zhu X, Zhang J, Baker SJ. mTor is required for hypertrophy of Pten-deficient neuronal soma in vivo. Proc Natl Acad Sci USA 100:12923-8, 2004.

Martin AC, Thornton JD, Liu J, Wang X, Zuo J, Jablonski MM, Chaum E, Zindy F, Skapek SX. Pathogenesis of persistent hyperplastic primary vitreous in mice lacking the arf tumor suppressor gene. Invest Ophthalmol Vis Sci 45:3387-96, 2004.

Cheatham MA, Huynh KH, Gao J, Zuo J, Dallos P. Cochlear function in Prestin knockout mice. J Physiol 560:821-30, 2004.

Tian Y, Li M, Fritzsch B, Zuo J. Creation of a transgenic mouse for hair-cell gene targeting by using a modified bacterial artificial chromosome containing Prestin. Dev Dyn 231:199-203, 2004.

Li M, Tian Y, Fritzsch B, Gao J, Wu X, Zuo J. Inner hair cell Cre-expressing transgenic mouse. Genesis 39:173-7, 2004.

Wu X, Gao J, Guo Y, Zuo J. Hearing threshold elevation precedes hair-cell loss in prestin knockout mice. Brain Res Mol Brain Res 126:30-7, 2004.

Piekorz RP, Gingras S, Hoffmeyer A, Ihle JN, Weinstein Y. Regulation of Progesterone Levels during Pregnancy and Parturition by Stat5 and 20{alpha}-Hydroxysteroid Dehydrogenase. Mol Endocrinol 2005 (in press).

Schuendeln MM, Piekorz RP, Wichmann C, Lee Y, McKinnon PJ, Boyd K, Takahashi Y, Ihle JN. The centrosomal, putative tumor suppressor protein TACC2 is dispensable for normal development, and deficiency does not lead to cancer. Mol Cell Biol 24:6403-9, 2004.

Carpino N, Thierfelder WE, Chang MS, Saris C, Turner SJ, Ziegler SF, Ihle JN. Absence of an essential role for thymic stromal lymphopoietin receptor in murine B-cell development. Mol Cell Biol 24:2584-92, 2004.

Carpino N, Turner S, Mekala D, Takahashi Y, Zang H, Geiger TL, Doherty P, Ihle JN. Regulation of ZAP-70 activation and TCR signaling by two related proteins, Sts-1 and Sts-2. Immunity 20:37-46, 2004.

Nilsson JA, Nilsson LM, Keller U, Yokota Y, Boyd K, Cleveland JL. Id2 is dispensable for myc-induced lymphomagenesis. Cancer Res 64:7296-301, 2004.

Nilsson JA, Cleveland JL. Mnt: master regulator of the Max network. Cell Cycle 3:588-90, 2004.

Nilsson JA, Maclean KH, Keller UB, Pendeville H, Baudino TA, Cleveland JL. Mnt loss triggers Myc transcription targets, proliferation, apoptosis, and transformation. Mol Cell Biol 24:1560-9, 2004

Kang-Decker N, Tong C, Boussouar F, Baker DJ, Xu W, Leontovich AA, Taylor WR, Brindle PK, van Deursen JM. Loss of CBP causes T cell lymphomagenesis in synergy with p27Kip1 insufficiency. Cancer Cell 5:177-89, 2004.

Loyd MR, Okamoto Y, Randall MS, Ney PA. Role of AP1/NFE2 binding sites in endogenous alpha-globin gene transcription. Blood 102:4223-8, 2003.

Sun W, Downing JR. Haploinsufficiency of AML1 results in a decrease in the number of LTR-HSCs while simultaneously inducing an increase in more mature progenitors. Blood 104:3565-3572, 2004.

Lorsbach RB, Moore J, Ang SO, Sun W, Lenny N, Downing JR. Role of RUNX1 in adult hematopoiesis: analysis of RUNX1-IRES-GFP knock-in mice reveals differential lineage expression. Blood 103:2522-9, 2004.

Li T, Inoue A, Lahti JM, Kidd VJ. Failure to proliferate and mitotic arrest of CDK11(p110/p58)-null mutant mice at the blastocyst stage of embryonic cell development. Mol Cell Biol 24:3188-97, 2004.

Zindy F, Williams RT, Baudino TA, Rehg JE, Skapek SX, Cleveland JL, Roussel MF, Sherr CJ. Arf tumor suppressor promoter monitors latent oncogenic signals in vivo. Proc Natl Acad Sci USA 100:15930-5, 2003.

Sherr CJ. An Arf(GFP/GFP) reporter mouse reveals that the Arf tumor suppressor monitors latent oncogenic signals in vivo. Cell Cycle 3:239-40, 2004.

Pestina TI, Jackson CW. Differential role of Stat5 isoforms in effecting hematopoietic recovery induced by Mpl-ligand in lethally myelosuppressed mice. Exp Hematol 31:1198-205, 2004.

Kitagawa R, Bakkenist CJ, McKinnon PJ, Kastan MB. Phosphorylation of SMC1 is a critical downstream event in the ATM-NBS1-BRCA1 pathway. Genes Dev 18:1423-38, 2004.

Parekh V, McEwen A, Barbour V, Takahashi Y, Rehg JE, Jane SM, Cunningham JM. Defective extraembryonic angiogenesis in mice lacking LBP-1a, a member of the grainyhead family of transcription factors. Mol Cell Biol 24:7113-29, 2004.

Krishnamurthy P, Ross DD, Nakanishi T, Bailey-Dell K, Zhou S, Mercer KE, Sarkadi B, Sorrentino BP, Schuetz JD. The stem cell marker Bcrp/ABCG2 enhances hypoxic cell survival through interactions with heme. J Biol Chem 279:24218-25, 2004.

Zhou S, Zong Y, Lu T, Sorrentino BP. Related Articles, Links  Hematopoietic cells from mice that are deficient in both Bcrp1/Abcg2 and Mdr1a/1b develop normally but are sensitized to mitoxantrone. Biotechniques 35:1248-52, 2003.

Jackowski S, Rehg JE, Zhang YM, Wang J, Miller K, Jackson P, Karim MA. Disruption of CCTbeta2 expression leads to gonadal dysfunction. Mol Cell Biol 24:4720-33, 2004.

Gingras S, Parganas E, de Pauw A, Ihle JN, Murray PJ. Re-examination of the role of SOCS1 in the regulation of Toll-like receptor signaling. J Biol Chem 2005 (in press).

Pauleau AL, Murray PJ. Role of nod2 in the response of macrophages to toll-like receptor agonists. Mol Cell Biol 23:7531-9, 2003.

Watanabe T, Kitani A, Murray PJ, Strober W. NOD2 is a negative regulator of Toll-like receptor 2-mediated T helper type 1 responses. Nat Immunol 5:800-8, 2004.

Assem M, Schuetz EG, Leggas M, Sun D, Yasuda K, Reid G, Zelcer N, Adachi M, Strom S, Evans RM, Moore DD, Borst P, Schuetz JD. Interactions between hepatic Mrp4 and Sult2a as revealed by the constitutive androstane receptor and Mrp4 knockout mice. J Biol Chem 279:22250-7, 2004.

Leggas M, Adachi M, Scheffer GL, Sun D, Wielinga P, Du G, Mercer KE, Zhuang Y, Panetta JC, Johnston B, Scheper RJ, Stewart CF, Schuetz JD. Mrp4 confers resistance to topotecan and protects the brain from chemotherapy. Mol Cell Biol 24:7612-21, 2004.

 

Last update: February 2005