The Mouse Molecular Technologies team provide high-throughput genotyping and characterisation of mutant mouse strains created either by targeted embryonic stem cells (ESC) or CRISPR/Cas9 gene editing in single-cell zygotes. Each strain contains an alteration in a single gene, the structure of which must be verified prior to breeding and phenotyping.
The mice are genotyped by either end-point PCR or real-time qPCR to determine how many copies of the mutant gene each individual posesses. Mice can then be bred to sufficient numbers and in the correct way for phenotyping
The Mouse Pipelines team is responsible for delivering the large-scale projects under its responsibility, including the Sanger 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
The main component of work our greatly contributes to the International Mouse Phenotyping Consortium, which aims to discover the function of all of the genes in the mouse genome that code for proteins by the use of a broad-spectrum standardised phenotyping platform and dataset. Our mouse strains and data are used by scientists throughout the world, reducing the amount of unnecessary experimental duplication and ensuring a 'gold standard' of models for research groups to study.
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.