Experts and Doctors on knockout mice in Freiburg, Baden Württemberg, Germany


Locale: Freiburg, Baden Württemberg, Germany
Topic: knockout mice

Top Publications

  1. Falk I, Potocnik A, Barthlott T, Levelt C, Eichmann K. Immature T cells in peripheral lymphoid organs of recombinase-activating gene-1/-2-deficient mice. Thymus dependence and responsiveness to anti-CD3 epsilon antibody. J Immunol. 1996;156:1362-8 pubmed
    ..These cells respond to CD3 signaling by aberrant maturation, possibly due to the inappropriate microenvironment of peripheral lymphoid organs. ..
  2. Lessmann E, Leitges M, Huber M. A redundant role for PKC-epsilon in mast cell signaling and effector function. Int Immunol. 2006;18:767-73 pubmed
    ..These results strongly suggest that PKC-epsilon plays a redundant role in MCs stimulated by antigen as well as other well-known MC stimuli. ..
  3. Roth E, Pircher H. IFN-gamma promotes Fas ligand- and perforin-mediated liver cell destruction by cytotoxic CD8 T cells. J Immunol. 2004;172:1588-94 pubmed
    ..Thus, our data suggest that IFN-gamma released by activated CD8 T cells upon Ag contact facilitates liver cell destruction. ..
  4. Kulik A, Vida I, Fukazawa Y, Guetg N, Kasugai Y, Marker C, et al. Compartment-dependent colocalization of Kir3.2-containing K+ channels and GABAB receptors in hippocampal pyramidal cells. J Neurosci. 2006;26:4289-97 pubmed
    ..Thus, Kir3 channels, localized to different subcellular compartments of hippocampal principal cells, appear to be differentially involved in synaptic integration in pyramidal cell dendrites. ..
  5. Stumpf M, Waskow C, Krötschel M, van Essen D, Rodriguez P, Zhang X, et al. The mediator complex functions as a coactivator for GATA-1 in erythropoiesis via subunit Med1/TRAP220. Proc Natl Acad Sci U S A. 2006;103:18504-9 pubmed
    ..In chromatin immunoprecipitation experiments, we find Mediator components at GATA-1-occupied enhancer sites. Thus, we conclude that Mediator subunit Med1 acts as a pivotal coactivator for GATA-1 in erythroid development. ..
  6. Huber M, Kalesnikoff J, Reth M, Krystal G. The role of SHIP in mast cell degranulation and IgE-induced mast cell survival. Immunol Lett. 2002;82:17-21 pubmed
    ..These studies demonstrate that mast cell sensitization by IgE is an active rather than a passive process. ..
  7. Baur N, Nerz G, Nil A, Eichmann K. Expression and selection of productively rearranged TCR beta VDJ genes are sequentially regulated by CD3 signaling in the development of NK1.1(+) alpha beta T cells. Int Immunol. 2001;13:1031-42 pubmed
    ..The data suggest that CD3 signals regulate initial TCR beta VDJ gene expression prior to beta selection in developing pre-NKT cells. ..
  8. Reinheckel T, Hagemann S, Dollwet Mack S, Martinez E, Lohmüller T, Zlatkovic G, et al. The lysosomal cysteine protease cathepsin L regulates keratinocyte proliferation by control of growth factor recycling. J Cell Sci. 2005;118:3387-95 pubmed
  9. Fiedler U, Reiss Y, Scharpfenecker M, Grunow V, Koidl S, Thurston G, et al. Angiopoietin-2 sensitizes endothelial cells to TNF-alpha and has a crucial role in the induction of inflammation. Nat Med. 2006;12:235-9 pubmed
    ..Ang-2 thereby acts as a switch of vascular responsiveness exerting a permissive role for the activities of proinflammatory cytokines. ..

More Information


  1. Heizmann B, Reth M, Infantino S. Syk is a dual-specificity kinase that self-regulates the signal output from the B-cell antigen receptor. Proc Natl Acad Sci U S A. 2010;107:18563-8 pubmed publisher
    ..This finding identifies Syk as a dual-specificity kinase and establishes a previously unexplored paradigm for the self-regulation of biological signaling processes. ..
  2. Aichele P, Unsoeld H, Koschella M, Schweier O, Kalinke U, Vucikuja S. CD8 T cells specific for lymphocytic choriomeningitis virus require type I IFN receptor for clonal expansion. J Immunol. 2006;176:4525-9 pubmed
    ..Lack of type I IFNR expression by P14 T cells did not affect cell division after LCMV infection but interfered with clonal expansion. Thus, direct type I IFN signaling is essential for CD8 T cell survival in certain viral infections. ..
  3. Su Y, Jumaa H. LAT links the pre-BCR to calcium signaling. Immunity. 2003;19:295-305 pubmed
    ..Together, our results suggest that the adaptor proteins LAT and SLP-76 are involved in pre-BCR signaling, thereby rescuing arrested murine SLP-65(-/-) pre-B cells. ..
  4. Kirsch M, Trautmann N, Ernst M, Hofmann H. Involvement of gp130-associated cytokine signaling in Müller cell activation following optic nerve lesion. Glia. 2010;58:768-79 pubmed publisher
    ..A potential role of CNTF was possibly masked by a compensatory increase in LIF signaling in the absence of CNTF. ..
  5. Mohrs M, Ledermann B, Kohler G, Dorfmüller A, Gessner A, Brombacher F. Differences between IL-4- and IL-4 receptor alpha-deficient mice in chronic leishmaniasis reveal a protective role for IL-13 receptor signaling. J Immunol. 1999;162:7302-8 pubmed
    ..major, mediated by a functional IL-13 receptor. ..
  6. Firat E, Saveanu L, Aichele P, Staeheli P, Huai J, Gaedicke S, et al. The role of endoplasmic reticulum-associated aminopeptidase 1 in immunity to infection and in cross-presentation. J Immunol. 2007;178:2241-8 pubmed
    ..Surprisingly, however, ERAP1 deficiency has no effect on cross-presentation of soluble OVA, suggesting that for soluble exogenous proteins, final processing may not take place in an environment containing active ERAP1. ..
  7. Siegers G, Swamy M, Fernández Malavé E, Minguet S, Rathmann S, Guardo A, et al. Different composition of the human and the mouse gammadelta T cell receptor explains different phenotypes of CD3gamma and CD3delta immunodeficiencies. J Exp Med. 2007;204:2537-44 pubmed
    ..Collectively, our results indicate that the different gammadelta T cell phenotypes between CD3gamma-deficient humans and mice can be explained by differences in their gammadelta TCR composition. ..
  8. Weckmann M, Collison A, Simpson J, Kopp M, Wark P, Smyth M, et al. Critical link between TRAIL and CCL20 for the activation of TH2 cells and the expression of allergic airway disease. Nat Med. 2007;13:1308-15 pubmed
    ..TRAIL is also increased in sputum of asthmatics. The function of TRAIL in the airway epithelium identifies this molecule as a target for the treatment of asthma. ..
  9. Kutejova E, Engist B, Self M, Oliver G, Kirilenko P, Bobola N. Six2 functions redundantly immediately downstream of Hoxa2. Development. 2008;135:1463-70 pubmed publisher
    ..We propose that Six2 acts to mediate Hoxa2 control over the insulin-like growth factor pathway during branchial arch development...
  10. Walter D, Schmich K, Vogel S, Pick R, Kaufmann T, Hochmuth F, et al. Switch from type II to I Fas/CD95 death signaling on in vitro culturing of primary hepatocytes. Hepatology. 2008;48:1942-53 pubmed publisher
    ..Our data suggest a selective crosstalk between extracellular matrix and Fas-mediated signaling that favors mitochondria-independent type I apoptosis induction. ..
  11. Knaus A, Muthig V, Schickinger S, Moura E, Beetz N, Gilsbach R, et al. Alpha2-adrenoceptor subtypes--unexpected functions for receptors and ligands derived from gene-targeted mouse models. Neurochem Int. 2007;51:277-81 pubmed
    ..4) Additional pharmacological targets for alpha2-adrenoceptor ligands were identified, e.g. inhibition of cardiac HCN2 and HCN4 pacemaker channels by clonidine. ..
  12. Dennemärker J, Lohmüller T, Mayerle J, Tacke M, Lerch M, Coussens L, et al. Deficiency for the cysteine protease cathepsin L promotes tumor progression in mouse epidermis. Oncogene. 2010;29:1611-21 pubmed publisher
    ..We conclude that Ctsl is critical for the termination of growth factor signaling in the endosomal/lysosomal compartment of keratinocytes and, therefore, functions as an anti-tumor protease. ..
  13. Haegel H, Larue L, Ohsugi M, Fedorov L, Herrenknecht K, Kemler R. Lack of beta-catenin affects mouse development at gastrulation. Development. 1995;121:3529-37 pubmed
    ..Our results demonstrate that, although beta-catenin is expressed rather ubiquitously, it is specifically required in the ectodermal cell layer. ..
  14. Sanos S, Bui V, Mortha A, Oberle K, Heners C, Johner C, et al. RORgammat and commensal microflora are required for the differentiation of mucosal interleukin 22-producing NKp46+ cells. Nat Immunol. 2009;10:83-91 pubmed publisher
    ..IL-22 released by these cells promoted the production of antimicrobial molecules important in the maintenance of mucosal homeostasis. ..
  15. Hagemann S, Gunther T, Dennemärker J, Lohmüller T, Bromme D, Schüle R, et al. The human cysteine protease cathepsin V can compensate for murine cathepsin L in mouse epidermis and hair follicles. Eur J Cell Biol. 2004;83:775-80 pubmed
  16. Nil A, Firat E, Sobek V, Eichmann K, Niedermann G. Expression of housekeeping and immunoproteasome subunit genes is differentially regulated in positively and negatively selecting thymic stroma subsets. Eur J Immunol. 2004;34:2681-9 pubmed
    ..The data suggest that negative selection may primarily involve immunoproteasome peptide repertoires and that peripheral infection may influence peptide repertoires involved in positive selection. ..
  17. Deussing J, Roth W, Saftig P, Peters C, Ploegh H, Villadangos J. Cathepsins B and D are dispensable for major histocompatibility complex class II-mediated antigen presentation. Proc Natl Acad Sci U S A. 1998;95:4516-21 pubmed
    ..Degradation of Ii proceeded normally in Cat B-/- splenocytes, as it did in Cat D-/- cells. We conclude that neither Cat B nor Cat D are essential for MHC class II-mediated antigen presentation. ..
  18. Boehm T, Scheu S, Pfeffer K, Bleul C. Thymic medullary epithelial cell differentiation, thymocyte emigration, and the control of autoimmunity require lympho-epithelial cross talk via LTbetaR. J Exp Med. 2003;198:757-69 pubmed
  19. Balkow S, Kersten A, Tran T, Stehle T, Grosse P, Museteanu C, et al. Concerted action of the FasL/Fas and perforin/granzyme A and B pathways is mandatory for the development of early viral hepatitis but not for recovery from viral infection. J Virol. 2001;75:8781-91 pubmed
  20. Flemming A, Brummer T, Reth M, Jumaa H. The adaptor protein SLP-65 acts as a tumor suppressor that limits pre-B cell expansion. Nat Immunol. 2003;4:38-43 pubmed
    ..Our results indicate that SLP-65 regulates a developmental program that promotes differentiation and limits pre-B cell expansion, thereby acting as a tumor suppressor. ..
  21. Merlin T, Woelky Bruggmann R, Fearns C, Freudenberg M, Landmann R. Expression and role of CD14 in mice sensitized to lipopolysaccharide by Propionibacterium acnes. Eur J Immunol. 2002;32:761-72 pubmed
    ..Therefore, hyperreactivity to LPS is characterized by an up-regulation of CD14, but the sensitization by P. acnes is not CD14 dependent. ..
  22. Benz C, Bleul C. A multipotent precursor in the thymus maps to the branching point of the T versus B lineage decision. J Exp Med. 2005;202:21-31 pubmed
    ..Thus, the newly identified precursor maps to the branching point of the T versus B lineage decision in the hematopoietic lineage hierarchy. ..
  23. Leemhuis J, Bouché E, Frotscher M, Henle F, Hein L, Herz J, et al. Reelin signals through apolipoprotein E receptor 2 and Cdc42 to increase growth cone motility and filopodia formation. J Neurosci. 2010;30:14759-72 pubmed publisher
    ..Our data link the observation that defects in Rho GTPases and Reelin signaling are responsible for developmental defects leading to neurological and psychiatric disorders. ..
  24. Cicko S, Lucattelli M, Müller T, Lommatzsch M, De Cunto G, Cardini S, et al. Purinergic receptor inhibition prevents the development of smoke-induced lung injury and emphysema. J Immunol. 2010;185:688-97 pubmed publisher
    ..We demonstrate, for the first time, that endogenous ATP contributes to smoke-induced lung inflammation and then development of emphysema via activation of the purinergic receptor subtypes, such as P2Y(2)R. ..
  25. Richter K, Hausmann J, Staeheli P. Interferon-gamma prevents death of bystander neurons during CD8 T cell responses in the brain. Am J Pathol. 2009;174:1799-807 pubmed publisher
  26. Huai J, Firat E, Nil A, Million D, Gaedicke S, Kanzler B, et al. Activation of cellular death programs associated with immunosenescence-like phenotype in TPPII knockout mice. Proc Natl Acad Sci U S A. 2008;105:5177-82 pubmed publisher
    ..Thus, TPPII is important for maintaining normal cellular and systemic physiology, which may be relevant for potential therapeutic applications of TPPII inhibitors. ..
  27. Vasiljeva O, Korovin M, Gajda M, Brodoefel H, Bojic L, Kruger A, et al. Reduced tumour cell proliferation and delayed development of high-grade mammary carcinomas in cathepsin B-deficient mice. Oncogene. 2008;27:4191-9 pubmed publisher
    ..Thus, our results indicate an in vivo role for Ctsb in promoting cellular anaplasia in mammary cancers and proliferation in lung metastases. ..
  28. Liese J, Schleicher U, Bogdan C. TLR9 signaling is essential for the innate NK cell response in murine cutaneous leishmaniasis. Eur J Immunol. 2007;37:3424-34 pubmed
    ..We conclude that TLR9 signaling is essential for NK cell activation, but dispensable for a protective T cell response to L. major in vivo. ..
  29. May P, Rohlmann A, Bock H, Zurhove K, Marth J, Schomburg E, et al. Neuronal LRP1 functionally associates with postsynaptic proteins and is required for normal motor function in mice. Mol Cell Biol. 2004;24:8872-83 pubmed
    ..Together, these findings suggest that LRP1, like other ApoE receptors, can modulate synaptic transmission in the brain. ..
  30. Krotkova A, Smith E, Nerz G, Falk I, Eichmann K. Delayed and restricted expression limits putative instructional opportunities of Vgamma1.1/Vgamma2 gammadelta TCR in alphabeta/gammadelta lineage choice in the thymus. J Immunol. 2004;173:25-32 pubmed
    ..1, and Vgamma2) appeared unselected in DN3. The results suggest a late and restricted expression of the corresponding gammadeltaTCR, severely limiting their putative instructional opportunities in alphabeta/gammadelta divergence. ..
  31. Koschella M, Voehringer D, Pircher H. CD40 ligation in vivo induces bystander proliferation of memory phenotype CD8 T cells. J Immunol. 2004;172:4804-11 pubmed
    ..In addition, we demonstrate that bona fide Ag-experienced memory CD8 T cells respond differently to anti-CD40-induced signals than memory phenotype CD8 T cells. ..
  32. Muthig V, Gilsbach R, Haubold M, Philipp M, Ivacevic T, Gessler M, et al. Upregulation of soluble vascular endothelial growth factor receptor 1 contributes to angiogenesis defects in the placenta of alpha 2B-adrenoceptor deficient mice. Circ Res. 2007;101:682-91 pubmed
  33. Moore R, Radice G, Dominis M, Kemler R. The generation and in vivo differentiation of murine embryonal stem cells genetically null for either N-cadherin or N- and P-cadherin. Int J Dev Biol. 1999;43:831-4 pubmed
  34. Nielsen P, Lorenz B, Muller A, Wenger R, Brombacher F, Simon M, et al. Altered erythrocytes and a leaky block in B-cell development in CD24/HSA-deficient mice. Blood. 1997;89:1058-67 pubmed
    ..Thus, apart from alterations in erythrocytes and a mild block in B-cell development, the regulated expression of HSA appears to be dispensable for the maturation and functioning of those cell lineages that normally express it. ..
  35. Tchaptchet S, Kirberg J, Freudenberg N, Schamel W, Galanos C, Freudenberg M. Innate, antigen-independent role for T cells in the activation of the immune system by Propionibacterium acnes. Eur J Immunol. 2010;40:2506-16 pubmed publisher
    ..Thus, under microbial pressure, different T-cell types, independent of their antigen specificity, exert NK-cell-like functions, which contribute decisively to the activation of the innate immune system. ..
  36. Ubelhart R, Bach M, Eschbach C, Wossning T, Reth M, Jumaa H. N-linked glycosylation selectively regulates autonomous precursor BCR function. Nat Immunol. 2010;11:759-65 pubmed publisher
    ..Our results suggest an unexpected mode of pre-BCR function, in which binding of the surrogate light chain to N46 mediates autonomous crosslinking and, concomitantly, receptor formation. ..
  37. Jumaa H, Wollscheid B, Mitterer M, Wienands J, Reth M, Nielsen P. Abnormal development and function of B lymphocytes in mice deficient for the signaling adaptor protein SLP-65. Immunity. 1999;11:547-54 pubmed
    ..Mutant B cells show reduced Ca2+ mobilization and reduced proliferative responses to B cell mitogens. We conclude that while playing an important role, SLP-65 is not always required for signaling from the BCR. ..
  38. Lausch E, Keppler R, Hilbert K, Cormier Daire V, Nikkel S, Nishimura G, et al. Mutations in MMP9 and MMP13 determine the mode of inheritance and the clinical spectrum of metaphyseal anadysplasia. Am J Hum Genet. 2009;85:168-78 pubmed publisher
  39. Tsurumi C, Firat E, Gaedicke S, Huai J, Mandal P, Niedermann G. Viability and DNA damage responses of TPPII-deficient Myc- and Ras-transformed fibroblasts. Biochem Biophys Res Commun. 2009;386:563-8 pubmed publisher
    ..Thus, our results do not support a generally important role of TPPII for viability and proliferation of transformed cells or their p53-mediated DNA damage response. ..
  40. Strauch O, Stypmann J, Reinheckel T, Martinez E, Haverkamp W, Peters C. Cardiac and ocular pathologies in a mouse model of mucopolysaccharidosis type VI. Pediatr Res. 2003;54:701-8 pubmed
    ..To our knowledge, these in vivo evaluations of heart function represent the first respective investigation of a MPS VI animal model and should provide a valuable measure for therapy studies in the MPS VI mouse. ..
  41. Mordstein M, Kochs G, Dumoutier L, Renauld J, Paludan S, Klucher K, et al. Interferon-lambda contributes to innate immunity of mice against influenza A virus but not against hepatotropic viruses. PLoS Pathog. 2008;4:e1000151 pubmed publisher
    ..From these results we conclude that IFN-lambda contributes to inborn resistance against viral pathogens infecting the lung but not the liver. ..
  42. Karnowski A, Achatz Straussberger G, Klockenbusch C, Achatz G, Lamers M. Inefficient processing of mRNA for the membrane form of IgE is a genetic mechanism to limit recruitment of IgE-secreting cells. Eur J Immunol. 2006;36:1917-25 pubmed
    ..Thus, we have identified a genetic steering mechanism in the regulation of IgE synthesis that represents a further means to restrain potentially dangerous, high serum IgE levels. ..
  43. Quaschning T, Voss F, Relle K, Kalk P, Vignon Zellweger N, Pfab T, et al. Lack of endothelial nitric oxide synthase promotes endothelin-induced hypertension: lessons from endothelin-1 transgenic/endothelial nitric oxide synthase knockout mice. J Am Soc Nephrol. 2007;18:730-40 pubmed
    ..The human ET+/+ eNOS-/- mice therefore represent a novel model of hypertension as a result of an imbalance between the vascular ET-1 and NO systems. ..
  44. Drakew A, Deller T, Heimrich B, Gebhardt C, Del Turco D, Tielsch A, et al. Dentate granule cells in reeler mutants and VLDLR and ApoER2 knockout mice. Exp Neurol. 2002;176:12-24 pubmed
  45. Kenzel S, Santos Sierra S, Deshmukh S, Moeller I, Ergin B, Fitzgerald K, et al. Role of p38 and early growth response factor 1 in the macrophage response to group B streptococcus. Infect Immun. 2009;77:2474-81 pubmed publisher
    ..In conclusion, MyD88, p38, and Egr-1, but not Elk-1, essentially mediate the inflammatory cytokine response to GBS organisms. ..
  46. Martins V, Boehm T, Bleul C. Ltbetar signaling does not regulate Aire-dependent transcripts in medullary thymic epithelial cells. J Immunol. 2008;181:400-7 pubmed
    ..We propose that the physiological medullary architecture ensures negative-selection by supporting lympho-epithelial interaction through a large epithelial cell surface distributed evenly across the medulla. ..
  47. Freudenberg M, Merlin T, Kalis C, Chvatchko Y, Stübig H, Galanos C. Cutting edge: a murine, IL-12-independent pathway of IFN-gamma induction by gram-negative bacteria based on STAT4 activation by Type I IFN and IL-18 signaling. J Immunol. 2002;169:1665-8 pubmed
    ..This pathway participates in the induction of IFN-gamma by Gram-negative bacteria and is therefore expected to play a role whenever IFN-alpha or IFN-beta and IL-18 are produced concomitantly during bacterial, viral, or other infections. ..
  48. Haidl I, Huber G, Eichmann K. An ADAM family member with expression in thymic epithelial cells and related tissues. Gene. 2002;283:163-70 pubmed
    ..Given its unique expression pattern and potential functions, murine ADAM28 may play a role in organogenesis and organ-specific functions such as thymic T cell development. ..
  49. Gilsbach R, Schneider J, Lother A, Schickinger S, Leemhuis J, Hein L. Sympathetic alpha(2)-adrenoceptors prevent cardiac hypertrophy and fibrosis in mice at baseline but not after chronic pressure overload. Cardiovasc Res. 2010;86:432-42 pubmed publisher
    ..However, these receptors are desensitized by chronic pressure overload which in turn may contribute to the pathogenesis of this condition. ..
  50. Huber M, Kalis C, Keck S, Jiang Z, Georgel P, Du X, et al. R-form LPS, the master key to the activation ofTLR4/MD-2-positive cells. Eur J Immunol. 2006;36:701-11 pubmed
  51. Firat E, Huai J, Saveanu L, Gaedicke S, Aichele P, Eichmann K, et al. Analysis of direct and cross-presentation of antigens in TPPII knockout mice. J Immunol. 2007;179:8137-45 pubmed
  52. Hetzer Egger C, Schorpp M, Haas Assenbaum A, Balling R, Peters H, Boehm T. Thymopoiesis requires Pax9 function in thymic epithelial cells. Eur J Immunol. 2002;32:1175-81 pubmed
    ..Whereas expression of TCRbeta chain genes is readily detectable in the mutant thymus, no expression of the TCRgamma chain was detectable. Our results identify a new genetically defined control point of thymopoiesis. ..
  53. Heinzel K, Bleul C. The Foxn1-dependent transcripts PCOLCE2 and mPPP1R16B are not required for normal thymopoiesis. Eur J Immunol. 2007;37:2562-71 pubmed
    ..While there is no evidence for a functional role of PCOLCE2 and mPPP1R16B in thymus development, our results suggest that the lack of thymopoiesis in Foxn1-deficient mice is caused by multiple functional defects. ..