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: Figure 1
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):

Bonegio RG, Beck LH, Kahlon RK, Lu W, Salant DJ. The fate of Notch-deficient nephrogenic progenitor cells during metanephric kidney development. Kidney Int 2011;79:1099-1112.

Jiang Z, Yu N, Kuang P, Chen M, Shao F, Martin G, Chui DH, Cardoso WV, Ai X, Lu J.J.   Trinucleotide Repeat Containing 6a (Tnrc6a)-Mediated microRNA Function Is Required for the Development of Yolk Sac Endoderm. Biol Chem. 2011 Dec 20.

Ward, JE, Ren R, Toraldo G, SooHoo P, Guan J, O’Hara C, Jasuja R, Trinkaus-Randall V, Liao R, Connors L, and Seldin D.  Doxycycline reduces fibril formation in a transgenic mouse model of AL amyloidosis.  Blood December 15, 2011 vol. 118 no. 25 6610-6617.

Kelly, JW. Finally, a transgenic light chain amyloidosis mouse model.  Blood 2011 118:6479-6480; doi:10.1182/blood-2011-10-386532.

L. Zeng, Y. Akasaki, K. Sato, N. Ouchi, Y. Izumiya, K. Walsh (2010). Insulin-like 6 is induced by muscle injury and functions as a regenerative factor. J. Biol. Chem. 285:36060-36069.

Koupenova M, Johnston-Cox H, Vezeridis A, Gavras H, Yang D, Zannis V, and Ravid K.  The A2b Adenosine Receptor Regulates Hyperlipidemia and Atherosclerosis.  Circulation.  2011 Dec 5.  [Epub Ahead of print].

Sommer CA, Sommer AG, Longmire TA, Christodoulou C, Thomas DD, Gostissa M, Alt FW, Murphy GJ, Kotton DN, Mostoslavsky G. Excision of reprogramming transgenes improves the differentiation potential of iPS cells generated with a single excisable vector.  Stem Cells. 2010 Jan;28(1):64-74.

Ouchi N, Asaumi Y, Ohashi K, Higuchi A, Sono-Romanelli S, Oshima Y, Walsh K.  DIP2A functions as a FSTL1 receptor.  J Biol Chem. 2010 Mar 5;285(10):7127-34. Epub 2010 Jan 6.

Izvolsky KI, Lu J, Martin G, Albrecht KH, Cardoso WV.  Systemic inactivation of Hs6st1 in mice is associated with late postnatal mortality without major defects in organogenesis.  Genesis. 2008 Jan;46(1):8-18. Erratum in: Genesis. 2008 Oct;46(10):574.

Eliades A, Papadantonakis N, Ravid K.  New roles for cyclin E in megakaryocytic polyploidization.  J Biol Chem. 2010 Apr 14. [Epub ahead of print]

Liu L, Brown D, McKee M, Lebrasseur NK, Yang D, Albrecht KH, Ravid K, Pilch PF.  Deletion of Cavin/PTRF causes global loss of caveolae, dyslipidemia, and glucose intolerance.  Cell Metab. 2008 Oct;8(4):310-7.

Liu L, Pilch PF.  A critical role of cavin (polymerase I and transcript release factor) in caveolae formation and organization.  J Biol Chem. 2008 Feb 15;283(7):4314-22. Epub 2007 Dec 3.

Sharov AA, Mardaryev AN, Sharova TY, Grachtchouk M, Atoyan R, Byers HR, Seykora JT, Overbeek P, Dlugosz A, Botchkarev VA.  Bone morphogenetic protein antagonist noggin promotes skin tumorigenesis via stimulation of the Wnt and Shh signaling pathways.  Am J Pathol. 2009 Sep;175(3):1303-14. Epub 2009 Aug 21.

Genzen JR, Yang D, Ravid K, Bordey A.  Activation of adenosine A2B receptors enhances ciliary beat frequency in mouse lateral ventricle ependymal cells.  Cerebrospinal Fluid Res. 2009 Nov 18;6:15.PMID: 19922651 [PubMed]Free

Ravid K.  MAL: not just a leukemia inducer. Blood. 2009 Nov 5;114(19):3977-8.  No abstract available. PMID: 19892723

Ravid K.  Megakaryocytes survive without survivin. Blood. 2009 Jul 2;114(1):4.PMID: 19574480 [PubMed]Related citations

McCrann DJ, Eliades A, Makitalo M, Matsuno K, Ravid K.  Differential expression of NADPH oxidases in megakaryocytes and their role in polyploidy. Blood. 2009 Aug 6;114(6):1243-9. Epub 2009 May 26.

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.

Boston University School of Medicine/Transgenic Knock Out Core Facility 


Scientific Director of Transgenic/Knock out Core, Dr. Katya Ravid
Transgenic Specialist and Manager, Greg Martin

Primary teaching affiliate
of BU School of Medicine