Mouse Genome Editing Unit

Group

Dr. Sagrario Ortega

Location

Centro Nacional de Investigaciones Oncológicas (CNIO), Madrid

Mouse Genome Editing Unit

The CNIO Mouse Genome Editing Unit is dedicated to the generation of genetically modified mouse models using state of the art technology in transgenesis, gene targeting and genome editing. Since the Unit was first launched in 2001, we have developed hundreds of gene-targeted alleles, knockout, knockin, inducible, conditional etc. by homologous recombination in mouse embryonic stem cells (ESCs). More recently, we have incorporated the CRISPR/Cas genome editing system, bypassing the need of ESCs for introducing these different gene targeted modifications directly in preimplantation embryos.

We are also interested in the biology of pluripotent stem cells, embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs) and in preimplantation mouse development and genetics. We have derived many ES cell lines de novo, from genetically modified mice and contributed to the establishment and characterization of mouse iPSCs. More recently we have been involved in exploring the potential of haploid mouse ES cells, derived from parthenogenetic mouse embryos, for genome wide genetic screenings and the identification of new cancer-related genes.

Our Unit has developed new mouse models to study the lymphatic system and its function in development and disease, particularly cancer and metastasis. We have created a knockin mouse for in vivo imaging of lymphangiogenesis. This mouse model, called “lymphoreporter”, enables monitoring lymphangiogenesis associated to processes such as inflammation and tissue regeneration by luminescence emission. The lymphoreporter mouse allows also the visualization and quantification of the response of lymph nodes and distant organs to systemic signals induced by tumors and tumor cells. We are interested in studying how this response, an early indicator of tumor metastasis, is involved in metastatic spread using this mouse model. In parallel, we have developed a second mouse model for Cre-mediated genetic modification specifically in lymphatic endothelial cells and used it to study gene function in LECs, lymphatic vessel development by lineage tracing and for creating models of lymphatic dysfunction such as lymphedema. We are currently using CRISPR-based genome-wide genetic screenings in lymphatic endothelial cells to identify new regulators of lymphangiogenesis.