Sagrario Ortega Head of Unit
T +34 917328000 (Ext 3170)
sortega@cnio.es

The laboratory mouse is the most widely used experimental model for genetic studies and preclinical drug development in cancer. The Mouse Genome Editing Unit is dedicated to the genetic edition of the mouse germ line and to the generation of genetically modified mouse strains. Hundreds of these strains have been created at our Unit. In many cases, they contain modifications that reproduce the genetic alterations found in human cancer and are introduced in the mouse to generate preclinical models of the disease, thereby contributing to the development of more efficient targeted therapies. Genetically modified mice are also created for testing in vivo, in a physiological context, hypothesis related to the molecular mechanisms that convert a normal cell to a malignant cell or that contribute to tumour expansion and invasion of distant organs, ultimately causing death. Cancer is an extremely complex disease that cannot be sufficiently well studied in vitro in a tissue culture plate. The generation of genetically modified mice is one of the basic pillars that sustain cancer research at the CNIO.

Publications

• Kataru RP, Ly CL, Shin J, Park HJ, Baik JE, Rehal S, Ortega S, Lyden D, Mehrara BJ (2019). Tumor Lymphatic Function Regulates Tumor Inflammatory and Immunosuppressive Microenvironments. Cancer Immunol Res (in press).
• Mayor-Ruiz C, Olbrich T, Drosten M, Lecona E, Vega-Sendino M, Ortega S, Dominguez O, Barbacid M, Ruiz S, Fernandez-Capetillo O (2018). ERF deletion rescues RAS deficiency in mouse embryonic stem cells. Genes Dev 32, 568-576.
• Lynch CJ, Bernad R, Calvo I, Nóbrega-Pereira S, Ruiz S, Ibarz N, Martinez-Val A, Graña-Castro O, Gómez-López G, Andrés-León E, Espinosa Angarica V, Del Sol A, Ortega S, Fernandez-Capetillo O, Rojo E, Munoz J, Serrano M (2018). The RNA Polymerase II Factor RPAP1 Is Critical for Mediator-Driven Transcription and Cell Identity. Cell Reports 22, 396-410.
• Villahoz S, Yunes-Leites PS, Méndez-Barbero N, Urso K, Bonzon-Kulichenko E, Ortega S, Nistal JF, Vazquez J, Offermanns S, Redondo JM, Campanero MR (2018). Conditional deletion of Rcan1 predisposes to hypertension-mediated intramural hematoma and subsequent aneurysm and aortic rupture. Nat Commun 9, 4795. Open Access
• Vilas JM, Carneiro C, Da Silva-Álvarez S, Ferreirós A, González P, Gómez M, Ortega S, Serrano M, García-Caballero T, González-Barcia M, Vidal A, Collado M (2018). Adult Sox2+ stem cell exhaustion in mice results in cellular senescence and premature aging. Aging Cell 17, e12834.
• Muñoz S, Búa S, Rodríguez-Acebes S, Megías D, Ortega S, de Martino A, Méndez J (2017). In Vivo DNA Re-replication Elicits Lethal Tissue Dysplasias.. Cell Reports 19, 928-938.
• Olmeda D, Cerezo-Wallis D, Riveiro-Falkenbach E, Pennacchi PC, Contreras-Alcalde M, Ibarz N, Cifdaloz M, Catena X, Calvo TG, Cañón E, Alonso-Curbelo D, Suarez J, Osterloh L, Graña O, Mulero F, Megías D, Cañamero M, Martínez-Torrecuadrada JL, Mondal C, Di Martino J, Lora D, Martinez-Corral I, Bravo-Cordero JJ, Muñoz J, Puig S, Ortiz-Romero P, Rodriguez-Peralto JL, Ortega S, Soengas MS (2017). Whole-body imaging of lymphovascular niches identifies pre-metastatic roles of midkine.. Nature 546, 676-680.
• Olbrich T, Mayor-Ruiz C, Vega-Sendino M, Gomez C, Ortega S, Ruiz S, Fernandez-Capetillo O. (2017). A p53-dependent response limits the viability of mammalian haploid cells.. Proc Natl Acad Sci USA 114, 9367-9372.
• Chirivella L, Kirstein M, Ferrón SR, Domingo-Muelas A, Durupt FC, Acosta-Umanzor C, Cano-Jaimez M, Pérez-Sánchez F, Barbacid M, Ortega S, Burks D, Fariñas I (2017). Cdk4 regulates adult neural stem cell proliferation and differentiation in response to insulin-IRS2 signals.. Stem Cells 35, 2403-2416.
• Calvete O, Varro A, Pritchard DM, Barroso A, Oteo M, Morcillo MÁ, Vargiu P, Dodd S, Garcia M, Reyes J, Ortega S, Benitez J (2016). A knockin mouse model for human ATP4aR703C mutation identified in familial gastric neuroendocrine tumors recapitulates the premalignant condition of the human disease and suggests new therapeutic strategies.. Dis Model Mech 9, 975-984.
• Ruiz S, Mayor-Ruiz C, Lafarga V, Murga M, Vega-Sendino M, Ortega S, Fernandez-Capetillo O (2016). A Genome-wide CRISPR Screen Identifies CDC25A as a Determinant of Sensitivity to ATR Inhibitors.. Mol Cell 62, 307-313.
• Augereau C, Collet L, Vargiu P, Guerra C, Ortega S, Lemaigre FP, Jacquemin P (2016). Chronic pancreatitis and lipomatosis are associated with defective function of ciliary genes in pancreatic ductal cells.. Hum Mol Genet 25, 5017-5026.
• Varela E, Muñoz-Lorente MA, Tejera AM, Ortega S, Blasco MA (2016). Generation of mice with longer and better preserved telomeres in the absence of genetic manipulations.. Nat Communications 7, 11739.
• Ahuja AK, Jodkowska K, Teloni F, Bizard AH, Zellweger R, Herrador R, Ortega S, Hickson ID, Altmeyer M, Mendez J, Lopes M (2016). A short G1 phase imposes constitutive replication stress and fork remodelling in mouse embryonic stem cells.. Nat Communications 7, 10660.
• Martinez-Corral I, Stanczuk L, Frye M, Ulvmar MH, Diegez-Hurtado R, Olmeda D, Makinen T, Ortega S (2016). Vegfr3-CreER T2 mouse, a new genetic tool for targeting the lymphatic system.. ANGIOGENESIS 19, 433-445.
• Huang JJ, Gardenier JC, Hespe GE, García Nores GD, Kataru RP, Ly CL, Martínez-Corral I, Ortega S, Mehrara BJ (2016). Lymph Node Transplantation Decreases Swelling and Restores Immune Responses in a Transgenic Model of Lymphedema.. PLoS ONE 11, e0168259.
• Gardenier JC, Hespe GE, Kataru RP, Savetsky IL, Torrisi JS, Nores GD, Dayan JJ, Chang D, Zampell J, Martínez-Corral I, Ortega S, Mehrara BJ (2016). Diphtheria toxin-mediated ablation of lymphatic endothelial cells results in progressive lymphedema.. JCI Insight 1, e84095.
• Búa S, Sotiropoulou P, Sgarlata C, Borlado, LR, Eguren M, Domínguez O, Ortega S, Malumbres M, Blanpain C, Méndez J (2015). Deregulated expression of Cdc6 in the skin facilitates papilloma formation and affects the hair growth cycle.. Cell Cycle 14, 3897-3907.
• Trakala M, Rodríguez-Acebes S, Maroto M, Symonds CE, Santamaría D, Ortega S, Barbacid M, Méndez J, Malumbres M. (2015). Functional reprogramming of polyploidization in megakaryocytes.. Dev Cell 32, 155-167.
• Viera A, Alsheimer M, Gómez R, Berenguer I, Ortega S, Symonds CE, Santamaría D, Benavente R, Suja JA (2015). CDK2 regulates nuclear envelope protein dynamics and telomere attachment in mouse meiotic prophase.. J Cell Sci 128, 88-99.
• Martinez-Corral I, Ulvmar MH, Stanczuk L, Tatin F, Kizhatil K, John SW, Alitalo K, Ortega S, Makinen T (2015). Nonvenous origin of dermal lymphatic vasculature.. Circ Res 116, 1649-1654.
• Stanczuk L, Martinez-Corral I, Ulvmar MH, Zhang Y, Laviña B, Fruttiger M, Adams RH, Saur D, Betsholtz C, Ortega S, Alitalo K, Graupera M, Mäkinen T (2015). cKit Lineage Hemogenic Endothelium-Derived Cells Contribute to Mesenteric Lymphatic Vessels.. Cell Reports (in press).
• López-Iglesias P, Alcaina Y, Tapia N, Sabour D, Arauzo-Bravo MJ, Sainz de la Maza D, Berra E, O'Mara AN, Nistal M, Ortega S, Donovan PJ, Schöler HR, De Miguel MP. (2015). Hypoxia induces pluripotency in primordial germ cells by HIF1a stabilization and Oct4 deregulation.. Antioxid Redox Sign 22, 205-223.
• Piazzolla D, Palla AR, Pantoja C, Cañamero M, de Castro IP, Ortega S, Gómez-López G, Dominguez O, Megías D, Roncador G, Luque-Garcia JL, Fernandez-Tresguerres B, Fernandez AF, Fraga MF, Rodriguez-Justo M, Manzanares M, Sánchez-Carbayo M, García-Pedrero JM, Rodrigo JP, Malumbres M, Serrano M (2014). Lineage-restricted function of the pluripotency factor NANOG in stratified epithelia.. Nat Communications 5, 4226.
• Jeltsch M, Jha SK, Tvorogov D, Anisimov A, Leppänen VM, Holopainen T, Kivelä R, Ortega S, Kärpanen T, Alitalo K (2014). CCBE1 enhances lymphangiogenesis via A disintegrin and metalloprotease with thrombospondin motifs-3-mediated vascular endothelial growth factor-C activation.. Circulation 129, 1962-1971.
• Aschen SZ, Farias-Eisner G, Cuzzone DA, Albano NJ, Ghanta S, Weitman ES, Ortega S, Mehrara BJ (2014). Lymph node transplantation results in spontaneous lymphatic reconnection and restoration of lymphatic flow.. Plast Reconstr Surg 133, 301-310.
• De Bonis ML, Ortega S, Blasco MA (2014). SIRT1 is necessary for proficient telomere elongation and genomic stability of induced pluripotent stem cells.. Stem Cell Reports 2, 690-706.
• Abad M, Mosteiro Ll, Pantoja C, Cañamero M, Rayon T, Ors I, Graña O, Megías D, Domínguez O, Martinez D, Manzanares M, Ortega S, Serrano M (2013). Reprogramming in vivo produces teratomas and iPS cells with totipotency features.. Nature 502, 340-345.
• Link J, Jahn D, Schmitt J, Göb E, Baar J, Ortega S, Benavente R, Alsheimer M (2013). The meiotic nuclear lamina regulates chromosome dynamics and promotes efficient homologous recombination in the mouse.. PLoS Genet 9, e1003261.
• Schneider RP, Garrobo I, Foronda M, Palacios JA, Marión RM, Flores I, Ortega S, Blasco MA (2013). TRF1 is a stem cell marker and is essential for the generation of induced pluripotent stem cells.. Nat Communications 4, 1946.