Boston University Medical Campus
Transgenic Facility

What is new in our facility (references and more)

WHAT IS NEW IN OUR FACILITY?

Example of available tools developed by investigators at BUSM with the transgenic core:

Example of an inducible system available on available on BALB/c strain:
The tGO transgene is a fusion protein made up of the cytoplasmic and TM domains of the transferring receptor and the immunogenic peptides of ovalbumin linked to a tetracycline regulated promoter. If these mice are bred to the Ii-rtTA transgenic line, and the resulting F1 offspring are fed doxycycline, the transgene is expressed in MHC class II+ cells. Expression of the transgene can be detected by injecting the mice with CSFE-labeled DO11 TCR transgenic T cells (reactive with valuing). CSFE is a fluorescent dye and the intensity of staining is diluted two fold every time a cell divides; this loss of fluorescence can be detected with a flow cytometer. Cell division and survival can be further monitored with the antibody KJ126 that reacts with the variable domains of the DO11 T cell receptor. As shown in the bottom panel of the figure, in doxycycline fed mice, the DO11 T cells undergo multiple divisions leading to a dramatic increase in cell number. The tGO mice can be bred to additional transgenic lines in which transactivator expression is regulated by an assortment of tissue specific promoters to establish model systems for the analysis of autoimmune disease. These studies were greatly facilitated by the ability of the Transgenic Core to inject the tGO construct directly into BALB/c oocytes. AMR07

A related web site with a description of available strains for inducible expression, produced by several other institutes:
tTA and rtTA effector mice
      http://www.zmg.uni-mainz.de/tetmouse/tet.htm

TetO-reporter strains and
      http://www.zmg.uni-mainz.de/tetmouse/strains.htm

Cre-inducible rtTA strains
      http://www.zmg.uni-mainz.de/tetmouse/strains.htm

Examples of recent publications of studies involving knock out/transgenic mice produced by our transgenic mouse core (a complete list is available in the core):

Tang X, Metzger D, Leeman S, Amar S. LPS-induced TNF-alpha factor (LITAF)-deficient mice express reduced LPS-induced cytokine: Evidence for LITAF-dependent LPS signaling pathways. Proc Natl Acad Sci U S A. 2006 Sep 12;103(37):13777-82. Epub 2006 Sep 5.

Yang D, Zhang Y, Nguyen HG, Koupenova M, Chauhan AK, Makitalo M, Jones MR, St Hilaire C, Seldin DC, Toselli P, Lamperti E, Schreiber BM, Gavras H, Wagner DD, Ravid K. The A2B adenosine receptor protects against inflammation and excessive vascular adhesion. J Clin Invest. 2006 Jul;116(7):1913-23.

Demicco EG, Kavanagh KT, Romieu-Mourez R, Wang X, Shin SR, Landesman-Bollag E, Seldin DC, Sonenshein GE. RelB/p52 NF-kappaB complexes rescue an early delay in mammary gland development in transgenic mice with targeted superrepressor IkappaB-alpha expression and promote carcinogenesis of the mammary gland. Mol Cell Biol. 2005 Nov;25(22):10136-47.

Taniyama Y, Ito M, Sato K, Kuester C, Veit K, Tremp G, Liao R, Colucci WS, Ivashchenko Y, Walsh K, Shiojima I. (2005) Akt3 overexpression in the heart results in progression from adaptive to maladaptive hypertrophy. J Mol Cell Cardiol. 38(2):375-85.

Yaar R, Jones MR, Chen JF, Ravid K. (2005) Animal models for the study of adenosine receptor function. J Cell Physiol. 202(1):9-20.

Nguyen, H.G., Yu, G., Makitalo, M., Yang, D., Xie, H-X, Jones, M.R., and Ravid, K. (2005) Conditional overexpression of transgenes in megakaryocytes and platelets in vivo. Blood 106:1559-1564.

Romieu-Mourez, R., D.W. Kim, S.M. Shin, E.G. Demicco, E. Landesman-Bollag , D.C. Seldin, R.D. Cardiff, and G.E. Sonenshein. Mouse Mammary Tumor Virus c-rel Transgenic Mice Develop Mammary Tumors. Molecular and Cellular Biology, 2004, 23(16): 5738-54.

Yang J, Sato K, Aprahamian T, Brown NJ, Hutcheson J, Bialik A, Perlman H, Walsh K. Endothelial overexpression of Fas ligand decreases atherosclerosis in apolipoprotein E-deficient mice. Arterioscler Thromb Vasc Biol. 2004 Aug; 24(8):1466-73. Epub 2004 Jun 03.

Yang J, Jones SP, Suhara T, Greer JJ, Ware PD, Nguyen NP, Perlman H, Nelson DP, Lefer DJ, Walsh K. Endothelial cell overexpression of fas ligand attenuates ischemia-reperfusion injury in the heart. J Biol Chem. 2003 Apr 25; 278(17):15185-91. Epub 2003 Feb 07.

Kan HY, Georgopoulos S, Zanni M, Shkodrani A, Tzatsos A, Xie HX, Zannis VI. Contribution of the hormone-response elements of the proximal ApoA-I promoter, ApoCIII enhancer, and C/EBP binding site of the proximal ApoA-I promoter to the hepatic and intestinal expression of the ApoA-I and ApoCIII genes in transgenic mice. Biochemistry. 2004, 4;43(17):5084-93.

Zhang Y, Nagata Y, Yu G, Nguyen HG, Jones MR, Toselli P, Jackson CW, Tatsuka M, Todokoro K, Ravid K. Aberrant quantity and localization of Aurora-B/AIM-1 and survivin during megakaryocyte polyploidization and the consequences of Aurora-B/AIM-1-deregulated xpreession. Blood. 2004 103(10):3717-26.

Jones MR, Zhao Z, Sullivan CP, Schreiber BM, Stone PJ, Toselli PA, Kagan HM, Cohen RA, Ravid K. A(3) adenosine receptor deficiency does not influence atherogenesis. J Cell Biochem. 2004 92(5):1034-43.

Wongtrakool C, Malpel S, Gorenstein J, Sedita J, Ramirez MI, Underhill TM, Cardoso WV. Downregulation of retinoic acid receptor- alpha signaling is required for type I cell formation and sacculation in the developing lung. J. Biol Chem. 2003, 278:46911-8.

Sharov, A.A., L. Weiner, T.Y. Sharova, F. Siebenhaar, R. Atpyan, A.M. Reginato, C.A. McNamara, K. Funa, B.A. Gilchrest, J.L. Brissette and V.A. Botchkarev. Noggin overexpression inhibits eyelid openng byaltering epidermal apoptosis and differentiation. EMBO J. 2003, 22(12):2992-3003.

Greenwald, R., J. R. Tumang, A. Sinha, N. Currier, R. D. Cardiff, T. L. Rothstein, D. V. Faller and G. V. Denis. Em-BRD2 transgenic mice develop B cell lymphoma and leukemia. Blood, 2003, 103: 1475 – 1484.

Romieu-Mourez, R., D.W. Kim, S.M. Shin, E. Landesman-Bollag, D. C. Seldin, R.D. Cardiff, and G.E. Sonenshein. MMTV-c-rel transgenic mice develop mammary tumors. Molecular and Cellular Biology, 2003, 23:5738-54.

Wang HD, Johns DG, Xu S, Cohen RA. (2002) Role of superoxide anion in regulating pressor and vascular hypertrophic response to angiotensin II.

Am J Physiol Heart Circ Physiol. 282(5):H1697-702.

Landesman-Bollag, E., R. Romieu-Mourez, D.H. Song, G.E. Sonenshein, R.D.Cardiff, and D.C. Seldin. Protein kinase CK2 in mammary gland tumorigenesis. Oncogene, 2001, 20:3247-57.

Factor, V., A.L. Oliver, S.S. Thorgeirsson, G.E. Sonenshein, & M.Arsura. Roles of Akt/PKB and IKK complex in constitutive induction of NF-kB in hepatocellular carcinomas of TGF-b/c-myc transgenic mice. Hepatol. 34:32-41 (2001).

Xu X, Toselli PA, Russell LD, Seldin DC. Globozoospermia in mice lacking the casein kinase II alpha’ catalytic subunit. Nat Genet. 1999 Sep;23(1):118-21.

Weiss N, Zhang YY, Heydrick S, Bierl C, Loscalzo J. Overexpression of cellular glutathione peroxidase rescues homocyst(e)ine-induced endothelial dysfunction. Proc Natl Acad Sci U S A. 2001 Oct 23;98(22):12503-8.