The Transgenic Technologies team is part of mouse pipelines and is repsonsible for the production of genetically modified mice. One of the most important tools at our scientific disposal in understanding mammalian gene function in the laboratory mouse. The fundamental genetic similarity between mice and humans allows researchers to infer a human gene's function based on studies with laboratory mice. One powerful technique is to turn off, or "knockout", the activity of a mouse gene to assess what biological systems are impacted. This gives insights how a similar gene in humans may contribute to disease when its activity is altered. The Transgenic Technologies mouse production team at the Sanger Institute contributes to this global effort by generating knock-out mice for the International Mouse Phenotyping Consortium as well as our own faculty scientists. We at all times consider animal welfare in our procedures and processes and follow the 3Rs' ethos of Replacement, Refinement and Reduction. All work performed using mice are tightly regulated by the Home Office.
The Mouse Pipelines team is responsible for delivering the large-scale projects under its responsibility, including the Sanger Institute Mouse Genetics Project , the National Institutes of Health KOMP2 production and phenotyping, the EUCOMMTools, and the Infrafrontier projects.
In addition the team is closely involved in three major Strategic Award projects funded by the Wellcome Trust: • Deciphering the Mechanisms of Developmental Disorders (DMDD) • Origins of Bone and Cartilage Disease (OBCD) • Immune function and pathology dissected by high-throughput analysis of mice with targeted gene disruptions – an investigation by the Infection and Immunity Immunophenotyping (3i) consortium.
We serve the scientific community with genetically altered strains of mice by supplying public repositories and researchers directly. Availability of these mouse strains is complemented by the standardised phenotypic characterisation performed by Mouse Pipelines, that is freely available to the scientific community. Accordingly, the research community continues to produce a growing scientific output using the resources distributed from the Mouse Pipelines at the Institute. To support this important part of our mission, we have an office to carry out cost-recovery.
The team researches and develops mouse resource production methods. For example we are implementing the use of the CRISPR mouse mutagenesis technology directly in mouse embryos, which will lead to great savings and acceleration of projects in their early phase by removing the need to use embryonic stem cells. We work flexibly so that we can rapidly shift our resources to advance all large-scale projects as needed while also supporting the needs of individual Faculty members.
We work closely with the Mouse Informatics and Research Support Facility teams to develop the Mouse Database. This work is essential for the welfare of our mice, to maintain optimal operational workflows, and to achieve our scientific goals, as well as for streamlining publication of our scientific results through the International Mouse Phenotyping Consortium (IMPC) web portal.
I work with a large team of superb scientists to generate mutant mouse strains carrying alleles of biomedical importance. Our work includes design of the mutation, mutagenesis of mouse ES cells, CRISPR mutagenesis, transgenic technologies to transfer the allele into the germline, molecular analysis and genotyping, colony management, cryopreservation, phenotypic analysis, and strain distribution.
Key Projects, Collaborations, Tools & Data
Mouse mutant lines are generated primarily for Sanger Institute Mouse Pipelines (formerly Mouse Genetics Project MGP). We have utilised these mutants in key international consortia collaborations such as the International Knockout Mouse Consortia (IKMC), International Mouse Phenotyping Consortia (IMPC), The European Conditional Mouse Mutagenesis Program (EUCOMM). All lines are then deposited and made freely available at The European Mouse Mutant Archive for further investigation by the wider scientifc community.
The Mouse Phenotyping team delivers phenotypic characterisation of mutant mice, typically knockouts of protein coding genes. Phenotyping encompasses a standardised set of more than 600 clinical parameters, and covers key biomedical areas such as reproduction, development, infection and immunity, musculoskeletal system, metabolism and endocrinology.