Mouse Molecular Technologies

Mouse Pipelines

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The team provided high-throughput genotyping and characterisation of mutant mouse strains created either by targeted embryonic stem cells or CRISPR/Cas9 gene editing

The Mouse Molecular Technologies team provided 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 contained an alteration in a single gene, the structure of which was verified prior to breeding and phenotyping.

The mice were genotyped by either end-point PCR or real-time qPCR to determine how many copies of the mutant gene each individual posessed. Mice were then bred to sufficient numbers and in the correct way for phenotyping

The Mouse Molecular Technologies team worked with the Mouse Genome Engineering, Mouse Transgenic Technologies and Mouse Phenotyping teams under the umbrella of Mouse Pipelines.

The Mouse Pipelines team was 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 was 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 served the scientific community with genetically altered strains of mice by supplying public repositories and researchers directly. Availability of these mouse strains was complemented by the standardised phenotypic characterisation performed by Mouse Pipelines, that was freely available to the scientific community. Accordingly, the research community continues to produce a growing scientific output using the resources generated by the Mouse Pipelines at the Institute. To support this important part of our mission, we had an office to carry out cost-recovery.

The team researched and developed mouse resource production methods. For example, we implemented the use of the CRISPR mouse mutagenesis technology directly in mouse embryos, which lead to great savings and acceleration of projects in their early phase by removing the need to use embryonic stem cells. We worked flexibly so that we could rapidly shift our resources to advance all large-scale projects as needed while also supporting the needs of individual Faculty members.

We worked closely with the Mouse Informatics and Research Support Facility teams to develop the Mouse Database. This work was 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.