Mouse Models in Immunology

We have extensive experience and a strong track record in the design of mouse models for inflammatory diseases such as hepatitis, nephritis or inflammatory bowel disease, autoimmune diseases such as systemic lupus erythematosus, joint disorders such as arthritis, allergy, and infections such as cholera, hepatitis, leishmaniasis or chlamydial infection.

We work closely with scientists from both academic institutions (Babraham Institute Cambridge, Dartmouth Medical School in New Hampshire, Frankfurt University, Geneva University Hospital, University of Illinois, Imperial College London, Institut Pasteur, University of Missouri-Columbia, etc.), pharmaceutical industries (Bayer Healthcare, Bristol-Myers Squibb, Janssen R&D, Novartis, Roche, etc.) or biotechnology companies.

We develop models for:

  • Studying immunological functions under both normal and pathologic conditions (thymic development, T-cell receptor, Interleukin or mast cell signaling, T-cell and neutrophil recruitment, wound healing, etc.).
  • Studying drug targets (humanization of CCRs or CD molecules, monitoring of cytokine responses or pathway activations, etc.).
  • Creating new tools for antibody production, labeled cells for trafficking studies, etc..

Do not hesitate to contact our scientific experts to discuss any project you have in mind. You will, at no expense to you, be able to evaluate what our experience, expertise and technologies for the design of genetically modified models will bring of value to your project.


Below you will find a selection of immunology models we have created for our clients:

Models for Immunological Conditions & Functions

Innate and adaptive immunity

Smallie T, Ross EA, Ammit AJ, Cunliffe HE, Tang T, Rosner DR, Ridley ML, Buckley CD, Saklatvala J, Dean JL, Clark AR.
Dual-Specificity Phosphatase 1 and Tristetraprolin Cooperate To Regulate Macrophage Responses to Lipopolysaccharide.
J Immunol. 2015 May 27.

Rodríguez C, López P, Pozo M, Duce AM, López-Pelaéz M, Fernández M, Alemany S.
COX2 expression and Erk1/Erk2 activity mediate Cot-induced cell migration.
Cell Signal. 2008

Immunodeficiency

Ménoret S, Fontanière S, Jantz D, Tesson L, Thinard R, Rémy S, Usal C, Ouisse LH, Fraichard A, Anegon I.
Generation of Rag1-knockout immunodeficient rats and mice using engineered meganucleases.
FASEB J. 2013

Autoimmunity

Automimmune encephalitis:
Borroto A, Arellano I, Blanco R, Fuentes M, Orfao A, Dopfer EP, Prouza M, Suchànek M, Schamel WW, Alarcón B
Relevance of Nck-CD3 epsilon interaction for T cell activation in vivo.
J Immunol. 2014

Systemic Lupus Erythematosus:
Steinmetz OM, Turner JE, Paust HJ, Lindner M, Peters A, Heiss K, Velden J, Hopfer H, Fehr S, Krieger T, Meyer-Schwesinger C, Meyer TN, Helmchen U, Mittrücker HW, Stahl RA, Panzer U.
CXCR3 mediates renal Th1 and Th17 immune response in murine lupus nephritis.
J Immunol. 2009

Inflammation

Atopic dermatitis (AD):
Yoon J, Leyva-Castillo JM, Wang G, Galand C, Oyoshi MK, Kumar L, Hoff S, He R, Chervonsky A, Oppenheim JJ, Kuchroo VK, van den Brink MR, Malefyt Rde W, Tessier PA, Fuhlbrigge R, Rosenstiel P, Terhorst C, Murphy G, Geha RS.
IL-23 induced in keratinocytes by endogenous TLR4 ligands polarizes dendritic cells to drive IL-22 responses to skin immunization.
J Exp Med. 2016

Crohn's disease:
Shih DQ, Zheng L, Zhang X, Zhang H, Kanazawa Y, Ichikawa R, Wallace KL, Chen J, Pothoulakis C, Koon HW, Targan SR
Inhibition of a novel fibrogenic factor Tl1a reverses established colonic fibrosis.
Mucosal Immunol. 2014

Chemotaxis:
McNeill E, Iqbal AJ, Patel J, White GE, Regan-Komito D, Greaves DR, Channon KM
Contrasting in vitro vs. in vivo effects of a cell membrane-specific CC-chemokine binding protein on macrophage chemotaxis.
J Mol Med (Berl). 2014

Arthritis:
Sun Y, Caplazi P, Zhang J, Mazloom A, Kummerfeld S, Quinones G, Senger K, Lesch J, Peng I, Sebrell A, Luk W, Lu Y, Lin Z, Barck K, Young J, Del Rio M, Lehar S9, Asghari V8, Lin W1, Mariathasan S9, DeVoss J1, Misaghi S10, Balazs M1, Sai T5, Haley B, Hass PE, Xu M, Ouyang W, Martin F, Lee WP, Zarrin AA
PILRα negatively regulates mouse inflammatory arthritis.
J Immunol. 2014

Lamacchia C, Palmer G, Seemayer CA, Talabot-Ayer D, Gabay C.
Enhanced Th1 and Th17 responses and arthritis severity in mice with a deficiency of myeloidcell-specific interleukin-1 receptor antagonist.
Arthritis Rheum. 2010

Inflammatory Bowel Disease:
Adolph TE, Tomczak MF, Niederreiter L, Ko HJ, Böck J, Martinez-Naves E, Glickman JN, Tschurtschenthaler M, Hartwig J, Hosomi S, Flak MB, Cusick JL, Kohno K, Iwawaki T, Billmann-Born S, Raine T, Bharti R, Lucius R, Kweon MN, Marciniak SJ, Choi A, Hagen SJ, Schreiber S, Rosenstiel P, Kaser A, Blumberg RS.
Paneth cells as a site of origin for intestinal inflammation.
Nature. 2013

Johswich K, Martin M, Bleich A, Kracht M, Dittrich-Breiholz O, Gessner JE, Suerbaum S, Wende E, Rheinheimer C, Klos A.
Role of the C5a receptor (C5aR) in acute and chronic dextran sulfate-induced models of inflammatory bowel disease.
Inflamm Bowel Dis. 2009

Nephritis:
Panzer U, Steinmetz OM, Paust HJ, Meyer-Schwesinger C, Peters A, Turner JE, Zahner G, Heymann F, Kurts C, Hopfer H, Helmchen U, Haag F, Schneider A, Stahl RA.
Chemokine receptor CXCR3 mediates T cell recruitment and tissue injury in nephrotoxic nephritis in mice.
J Am Soc Nephrol. 2007

Vascular inflammation:
Hahm E, Li J, Kim K, Huh S, Rogelj S, Cho J.
Extracellular protein disulfide isomerase regulates ligand-binding activity of αMβ2 integrin and neutrophil recruitment during vascular inflammation.
Blood. 2013

Necroptosis:
Newton K, Dugger DL, Maltzman A, Greve JM, Hedehus M, Martin-McNulty B, Carano RA, Cao TC, van Bruggen N, Bernstein L, Lee WP, Wu X, DeVoss J, Zhang J, Jeet S, Peng I, McKenzie BS, Roose-Girma M, Caplazi P, Diehl L, Webster JD, Vucic D.
RIPK3 deficiency or catalytically inactive RIPK1 provides greater benefit than MLKL deficiency in mouse models of inflammation and tissue injury.
Cell Death Differ. 2016 May 13.

Newton K, Dugger DL, Wickliffe KE, Kapoor N, de Almagro MC, Vucic D, Komuves L, Ferrando RE, French DM, Webster J, Roose-Girma M, Warming S, Dixit VM
Activity of protein kinase RIPK3 determines whether cells die by necroptosis or apoptosis.
Science. 2014

Wound healing:
Crowe J, Aubareda A, McNamee K, Przybycien PM, Lu X, Williams RO, Bou-Gharios G, Saklatvala J, Dean JL.
Heat Shock Protein B1-Deficient Mice Display Impaired Wound Healing.
PlosOne. 2013

IL-1R antagonist:
Lamacchia C, Palmer G, Bischoff L, Rodriguez E, Talabot-Ayer D, Gabay C.
Distinct roles of hepatocyte- and myeloid cell-derived IL-1 receptor antagonist during endotoxemia and sterile inflammation in mice.
J Immunol. 2010

Allergy

Dioszeghy V, Mondoulet L, Dhelft V, Ligouis M, Puteaux E, Dupont C, Benhamou PH
The regulatory T cells induction by Epicutaneous immunotherapy is sustained and mediates long term protection from eosinophilic disorders in peanut sensitized mice.
Clin Exp Allergy. 2014

Pushparaj PN, Manikandan J, Tay HK, H'ng SC, Kumar SD, Pfeilschifter J, Huwiler A, Melendez AJ.
Sphingosine kinase 1 is pivotal for Fc epsilon RI-mediated mast cell signaling and functional responses in vitro and in vivo.
J Immunol. 2009

Infection

Salmonella typhimurium:
Qu Y, Misaghi S, Newton K, Maltzman A, Izrael-Tomasevic A, Arnott D, Dixit VM.
NLRP3 recruitment by NLRC4 during Salmonella infection.
J Exp Med. 2016

Cholera:
Kim D, Kim YG, Seo SU, Kim DJ, Kamada N, Prescott D, Philpott DJ, Rosenstiel P, Inohara N, Núñez G.
Nod2-mediated recognition of the microbiota is critical for mucosal adjuvant activity of cholera toxin.
Nat Med. 2016

Hepatitis:
Lamacchia C, Rodriguez E, Palmer G, Vesin C, Seemayer CA, Rubbia-Brandt L, Gabay C.
Mice deficient in hepatocyte-specific IL-1Ra show delayed resolution of concanavalin A-induced hepatitis.
Eur J Immunol. 2012

Leishmania:
Al-Mutairi MS, Cadalbert LC, McGachy HA, Shweash M, Schroeder J, Kurnik M, Sloss CM, Bryant CE, Alexander J, Plevin R.
MAP kinase phosphatase-2 plays a critical role in response to infection by Leishmania mexicana.
PLoS Pathog. 2010

Chlamydia:
Abdul-Sater AA, Saïd-Sadier N, Lam VM, Singh B, Pettengill MA, Soares F, Tattoli I, Lipinski S, Girardin SE, Rosenstiel P, Ojcius DM.
Enhancement of reactive oxygen species production and chlamydial infection by the mitochondrial Nod-like family member NLRX1.
J Biol Chem. 2010

Thymic development

Borroto A, Arellano I, Dopfer EP, Prouza M, Suchànek M, Fuentes M, Orfao A, Schamel WW, Alarcón B.
Nck Recruitment to the TCR Required for ZAP70 Activation during Thymic Development.
J Immunol. 2013

Haymaker CL, Guloglu FB, Cascio JA, Hardaway JC, Dhakal M, Wan X, Hoeman CM, Zaghouani S, Rowland LM, Tartar DM, VanMorlan AM, Zaghouani H.
Bone marrow-derived IL-13Rα,1-positive thymic progenitors are restricted to the myeloid lineage.
J Immunol. 2012

Drug targeting

Needham LA, Davidson AH, Bawden LJ, Belfield A, Bone EA, Brotherton DH, Bryant S, Charlton MH, Clark VL, Davies SJ, Donald A, Day FA, Krige D, Legris V, McDermott J, McGovern Y, Owen J, Patel SR, Pintat S, Testar RJ, Wells GM, Moffat D, Drummond AH.
Drug targeting to monocytes and macrophages using esterase-sensitive chemical motifs.
J Pharmacol Exp Ther. 2011

Model Creation Services

Conditional Knockout (Learn more):
Yoon J, Leyva-Castillo JM, Wang G, Galand C, Oyoshi MK, Kumar L, Hoff S, He R, Chervonsky A, Oppenheim JJ, Kuchroo VK, van den Brink MR, Malefyt Rde W, Tessier PA, Fuhlbrigge R, Rosenstiel P, Terhorst C, Murphy G, Geha RS.
IL-23 induced in keratinocytes by endogenous TLR4 ligands polarizes dendritic cells to drive IL-22 responses to skin immunization.
J Exp Med. 2016

Kim D, Kim YG, Seo SU, Kim DJ, Kamada N, Prescott D, Philpott DJ, Rosenstiel P, Inohara N, Núñez G.
Nod2-mediated recognition of the microbiota is critical for mucosal adjuvant activity of cholera toxin.
Nat Med. 2016

Adolph TE, Tomczak MF, Niederreiter L, Ko HJ, Böck J, Martinez-Naves E, Glickman JN, Tschurtschenthaler M, Hartwig J, Hosomi S, Flak MB, Cusick JL, Kohno K, Iwawaki T, Billmann-Born S, Raine T, Bharti R, Lucius R, Kweon MN, Marciniak SJ, Choi A, Hagen SJ, Schreiber S, Rosenstiel P, Kaser A, Blumberg RS.
Paneth cells as a site of origin for intestinal inflammation.
Nature. 2013

Hahm E, Li J, Kim K, Huh S, Rogelj S, Cho J.
Extracellular protein disulfide isomerase regulates ligand-binding activity of αMβ2 integrin and neutrophil recruitment during vascular inflammation.
Blood. 2013

Constitutive Knockout (Learn more):
Lamacchia C, Rodriguez E, Palmer G, Vesin C, Seemayer CA, Rubbia-Brandt L, Gabay C.
Mice deficient in hepatocyte-specific IL-1Ra show delayed resolution of concanavalin A-induced hepatitis.
Eur J Immunol. 2012

Safe Knockout (Learn more):
Crowe J, Aubareda A, McNamee K, Przybycien PM, Lu X, Williams RO, Bou-Gharios G, Saklatvala J, Dean JL.
Heat Shock Protein B1-Deficient Mice Display Impaired Wound Healing.
PlosOne. 2013

Reporter/Tag Knockin (Learn more):
Dioszeghy V, Mondoulet L, Dhelft V, Ligouis M, Puteaux E, Dupont C, Benhamou PH
The regulatory T cells induction by Epicutaneous immunotherapy is sustained and mediates long term protection from eosinophilic disorders in peanut sensitized mice.
Clin Exp Allergy. 2014

Haymaker CL, Guloglu FB, Cascio JA, Hardaway JC, Dhakal M, Wan X, Hoeman CM, Zaghouani S, Rowland LM, Tartar DM, VanMorlan AM, Zaghouani H.
Bone marrow-derived IL-13Rα,1-positive thymic progenitors are restricted to the myeloid lineage.
J Immunol. 2012

Point Mutation Knockin (Learn more):
Newton K, Dugger DL, Wickliffe KE, Kapoor N, de Almagro MC, Vucic D, Komuves L, Ferrando RE, French DM, Webster J, Roose-Girma M, Warming S, Dixit VM
Activity of protein kinase RIPK3 determines whether cells die by necroptosis or apoptosis.
Science. 2014

Borroto A, Arellano I, Dopfer EP, Prouza M, Suchànek M, Fuentes M, Orfao A, Schamel WW, Alarcón B.
Nck Recruitment to the TCR Required for ZAP70 Activation during Thymic Development.
J Immunol. 2013

Permissive Locus HPRT Knockin (Learn more):
McNeill E, Iqbal AJ, Patel J, White GE, Regan-Komito D, Greaves DR, Channon KM
Contrasting in vitro vs. in vivo effects of a cell membrane-specific CC-chemokine binding protein on macrophage chemotaxis.
J Mol Med (Berl). 2014

Needham LA, Davidson AH, Bawden LJ, Belfield A, Bone EA, Brotherton DH, Bryant S, Charlton MH, Clark VL, Davies SJ, Donald A, Day FA, Krige D, Legris V, McDermott J, McGovern Y, Owen J, Patel SR, Pintat S, Testar RJ, Wells GM, Moffat D, Drummond AH.
Drug targeting to monocytes and macrophages using esterase-sensitive chemical motifs.
J Pharmacol Exp Ther. 2011