Mouse Genome Editing Core Unit

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

Graduate Students

Aleida Pujol
Daniel Serrano

Technicians

Estefania Ayala
Marina Cabrerizo
Carmen Gómez
Jaime Muñoz
Patricia Prieto
Pierfrancesco Vargiu

Genetically modified mice represent one of the basic pillars that sustain cancer research at the CNIO. The term ‘cancer’ includes a variety of extremely complex diseases in which malignant cells communicate with different body systems, such as immune cells or blood vessels, that modulate tumour growth, expansion and invasion. Such complexity cannot be sufficiently well studied by using in vitro systems alone.

The Mouse Genome Editing Unit is dedicated to the design, generation and cryopreservation of genetically modified mouse models of cancer, using state-of-the-art technology for the controlled modification of the mouse germ line. In collaboration with CNIO groups, we have created hundreds of genetically engineered mouse strains that are crucial for understanding the molecular basis of tumour development and for the preclinical validation of new and more efficient cancer therapies. The Unit currently maintains a collection of more than 1000 cryopreserved mouse strains from which the entire scientific community may benefit for the advancement of Science in many different research disciplines.

Publications

Miguel V, Tituaña J, Herrero JI, Herrero L, Serra D, Cuevas P, Barbas C, Puyol DR, Márquez-Expósito L, Ruiz-Ortega M, Castillo C, Sheng X, Susztak K, Ruiz-Canela M, Salas-Salvadó J, González MAM, Ortega S, Ramos R, Lamas S (2021). Renal tubule Cpt1a overexpression protects from kidney fibrosis by restoring mitochondrial homeostasis. J Clin Invest 131, e140695. CNIO Publication.
Salazar-Roa M, Trakala M, Álvarez-Fernández M, Valdés-Mora F, Zhong C, Muñoz J, Yu Y, Peters TJ, Graña-Castro O, Serrano R, Zapatero-Solana E, Abad M, Bueno MJ, de Cedrón MG, Fernández-Piqueras J, Serrano M, Blasco MA, Wang DZ, Clark SJ, Izpisua-Belmonte JC, Ortega S, Malumbres M (2020). Transient Exposure to miR-203 Enhances the Differentiation Capacity of Established Pluripotent Stem Cells. EMBO J 39, e104324. CNIO Publication.
Lynch CJ, Bernad R, Martínez-Val A, Shahbazi MN, Nóbrega-Pereira S, Calvo I, Blanco-Aparicio C, Tarantino C, Garreta E, Richart-Ginés L, Alcazar N, Graña-Castro O, Gómez-Lopez G, Aksoy I, Muñoz-Martín M, Martinez S, Ortega S, Prieto S, Simboeck E, Camasses A, Stephan-Otto Attolini C, Fernandez AF, Sierra MI, Fraga MF, Pastor J, Fisher D, Montserrat N, Savatier P, Muñoz J, Zernicka-Goetz M, Serrano M (2020). Global hyperactivation of enhancers stabilizes human and mouse naive pluripotency through inhibition of CDK8/19 Mediator kinases. Nat Cell Biol 22, 1223-1238. CNIO Publication.
Lioux G, Liu X, Temiño S, Oxendine M, Ayala E, Ortega S, Kelly RG, Oliver G, Torres M (2020). A second heart field-derived vasculogenic niche contributes to cardiac lymphatics. Dev Cell 52, 350-363. CNIO Publication.
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 7, 1345-1358. CNIO Publication.
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. CNIO Publication. Open Access
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. CNIO Publication. Open Access
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. CNIO Publication. 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. CNIO Publication. Open Access
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. CNIO Publication.
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. CNIO Publication.
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. CNIO Publication.
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. CNIO Publication.
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. CNIO Publication.
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. CNIO Publication.
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. CNIO Publication.
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 Commun 7, 11739. CNIO Publication. Open Access
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 Commun 7, 10660. CNIO Publication. Open Access
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. CNIO Publication.
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. CNIO Publication.
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. CNIO Publication.