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

The laboratory mouse is the experimental model of choice for genetic studies and preclinical drug development in cancer. The Transgenic Mice Unit is dedicated to the genetic edition of the mouse germ line and to the generation of genetically modified mouse strains. Hundreds of mouse genes have been specifically modified at our Unit. In many cases, these modifications reproduce the genetic alterations found in human cancers and are introduced in the mouse to generate preclinical models of the disease, thereby contributing to the development of more efficient targeted therapies. In other instances, genetically modified mice are created for testing hypothesis in vivo, in a physiological context, with the aim of gaining new insight into the molecular mechanisms responsible for converting a normal cell into a malignant cell or for making a tumour grow and expand and subsequently invade other organs and become deadly. Cancer is an extremely complex disease that cannot be sufficiently studied in a tissue culture plate. The generation of genetically modified mice is one of the basic pillars on which cancer research at the CNIO is based.

Publications

• ERF deletion rescues RAS deficiency in mouse embryonic stem cells.(2018)
  Mayor-Ruiz C, Olbrich T, Drosten M, Lecona E, Vega-Sendino M, Ortega S, Dominguez O, Barbacid M, Ruiz S, Fernandez-Capetillo O.
  Genes Dev 32, 568-576.
• The RNA Polymerase II Factor RPAP1 Is Critical for Mediator-Driven Transcription and Cell Identity.(2018)
  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
  Cell Reports 22, 396-410.
• Conditional deletion of Rcan1 predisposes to hypertension-mediated intramural hematoma and subsequent aneurysm and aortic rupture.(2018)
  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
  Nat Commun 9, 4795-.
• Adult Sox2+ stem cell exhaustion in mice results in cellular senescence and premature aging.(2018)
  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
  Aging Cell 17, e12834-.
• Whole-body imaging of lymphovascular niches identifies pre-metastatic roles of midkine.(2017)
  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
  Nature 546, 676-680.
• Cdk4 regulates adult neural stem cell proliferation and differentiation in response to insulin-IRS2 signals.(2017)
  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
  Stem Cells 35, 2403-2416.
• In Vivo DNA Re-replication Elicits Lethal Tissue Dysplasias.(2017)
  Muñoz S, Búa S, Rodríguez-Acebes S, Megías D, Ortega S, de Martino A, Méndez J
  Cell Reports 19, 928-938.
• A p53-dependent response limits the viability of mammalian haploid cells.(2017)
  Olbrich T, Mayor-Ruiz C, Vega-Sendino M, Gomez C, Ortega S, Ruiz S, Fernandez-Capetillo O.
  Proc Natl Acad Sci USA 114, 9367-9372.
• Generation of mice with longer and better preserved telomeres in the absence of genetic manipulations.(2016)
  Varela E, Muñoz-Lorente MA, Tejera AM, Ortega S, Blasco MA
  Nat Communications 7, 11739-.
• 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.(2016)
  Calvete O, Varro A, Pritchard DM, Barroso A, Oteo M, Morcillo MÁ, Vargiu P, Dodd S, Garcia M, Reyes J, Ortega S, Benitez J
  Dis Model Mech 9, 975-984.
• Chronic pancreatitis and lipomatosis are associated with defective function of ciliary genes in pancreatic ductal cells.(2016)
  Augereau C, Collet L, Vargiu P, Guerra C, Ortega S, Lemaigre FP, Jacquemin P
  Hum Mol Genet 25, 5017-5026.
• A Genome-wide CRISPR Screen Identifies CDC25A as a Determinant of Sensitivity to ATR Inhibitors.(2016)
  Ruiz S, Mayor-Ruiz C, Lafarga V, Murga M, Vega-Sendino M, Ortega S, Fernandez-Capetillo O
  Mol Cell 62, 307-313.
• A short G1 phase imposes constitutive replication stress and fork remodelling in mouse embryonic stem cells.(2016)
  Ahuja AK, Jodkowska K, Teloni F, Bizard AH, Zellweger R, Herrador R, Ortega S, Hickson ID, Altmeyer M, Mendez J, Lopes M
  Nat Communications 7, 10660-.
• Vegfr3-CreER T2 mouse, a new genetic tool for targeting the lymphatic system.(2016)
  Martinez-Corral I, Stanczuk L, Frye M, Ulvmar MH, Diegez-Hurtado R, Olmeda D, Makinen T, Ortega S
  ANGIOGENESIS 19, 433-445.
• Lymph Node Transplantation Decreases Swelling and Restores Immune Responses in a Transgenic Model of Lymphedema.(2016)
  Huang JJ, Gardenier JC, Hespe GE, García Nores GD, Kataru RP, Ly CL, Martínez-Corral I, Ortega S, Mehrara BJ
  PLoS ONE 11, e0168259-.
• Diphtheria toxin-mediated ablation of lymphatic endothelial cells results in progressive lymphedema.(2016)
  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
  JCI Insight 1, e84095-.
• Functional reprogramming of polyploidization in megakaryocytes.(2015)
  Trakala M, Rodríguez-Acebes S, Maroto M, Symonds CE, Santamaría D, Ortega S, Barbacid M, Méndez J, Malumbres M.
  Dev Cell 32, 155-167.
• CDK2 regulates nuclear envelope protein dynamics and telomere attachment in mouse meiotic prophase.(2015)
  Viera A, Alsheimer M, Gómez R, Berenguer I, Ortega S, Symonds CE, Santamaría D, Benavente R, Suja JA
  J Cell Sci 128, 88-99.
• Deregulated expression of Cdc6 in the skin facilitates papilloma formation and affects the hair growth cycle.(2015)
  Búa S, Sotiropoulou P, Sgarlata C, Borlado, LR, Eguren M, Domínguez O, Ortega S, Malumbres M, Blanpain C, Méndez J
  Cell Cycle 14, 3897-3907.
• Nonvenous origin of dermal lymphatic vasculature.(2015)
  Martinez-Corral I, Ulvmar MH, Stanczuk L, Tatin F, Kizhatil K, John SW, Alitalo K, Ortega S, Makinen T
  Circ Res 116, 1649-1654.
• cKit Lineage Hemogenic Endothelium-Derived Cells Contribute to Mesenteric Lymphatic Vessels.(2015)
  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
  Cell Reports (in press).
• Hypoxia induces pluripotency in primordial germ cells by HIF1a stabilization and Oct4 deregulation.(2015)
  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.
  Antioxid Redox Sign 22, 205-223.
• SIRT1 is necessary for proficient telomere elongation and genomic stability of induced pluripotent stem cells.(2014)
  De Bonis ML, Ortega S, Blasco MA
  Stem Cell Reports 2, 690-706.
• Lineage-restricted function of the pluripotency factor NANOG in stratified epithelia.(2014)
  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
  Nat Communications 5, 4226-.
• CCBE1 enhances lymphangiogenesis via A disintegrin and metalloprotease with thrombospondin motifs-3-mediated vascular endothelial growth factor-C activation.(2014)
  Jeltsch M, Jha SK, Tvorogov D, Anisimov A, Leppänen VM, Holopainen T, Kivelä R, Ortega S, Kärpanen T, Alitalo K
  Circulation 129, 1962-1971.
• Lymph node transplantation results in spontaneous lymphatic reconnection and restoration of lymphatic flow.(2014)
  Aschen SZ, Farias-Eisner G, Cuzzone DA, Albano NJ, Ghanta S, Weitman ES, Ortega S, Mehrara BJ
  Plast Reconstr Surg 133, 301-310.
• TRF1 is a stem cell marker and is essential for the generation of induced pluripotent stem cells.(2013)
  Schneider RP, Garrobo I, Foronda M, Palacios JA, Marión RM, Flores I, Ortega S, Blasco MA
  Nat Communications 4, 1946-.
• Reprogramming in vivo produces teratomas and iPS cells with totipotency features.(2013)
  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
  Nature 502, 340-345.
• The meiotic nuclear lamina regulates chromosome dynamics and promotes efficient homologous recombination in the mouse.(2013)
  Link J, Jahn D, Schmitt J, Göb E, Baar J, Ortega S, Benavente R, Alsheimer M
  PLoS Genet 9, e1003261-.