The IMPC has 21 international phenotyping centres who use high throughput pipelines to systematically phenotype knockout mouse strains. These centres are generating homozygous knockout mouse strains using standardised allele production for every protein coding gene in the mouse genome, producing seven males and seven females per gene.
Our phenotyping pipelines are an exemplar of high-throughput pipelines for the acquisition of broad-based phenotype data at both embryonic and adult time points. The range of phenotyping platforms ensures the recovery of phenotype data across multiple systems and disease states.
At eight weeks, mice undergo fertility, viability and embryonic phenotyping. Viability is a key step in this process and determines what further phenotyping tests and pipelines the line will undertake.
If a knockout line is homozygous lethal or subviable then it will undergo the embryonic pipeline. The embryonic pipeline aims to establish the window of lethality of the embryos and includes various imaging techniques to identify abnormalities in developing embryos. Homozygous and heterozygous viable lines will undergo the early adult pipeline between weeks 9 to 16. At week 16 knockout lines are terminated and undergo tissue collection and pathology.
Wild-type mice are also bred and continuously phenotyped to create a strong, reliable and growing standard dataset against which the knockout mouse lines are compared. Wild-type mice, therefore, undergo the same early adult pipeline as viable knockout lines. 10% of these mice are further aged and between weeks 49 and 70 will undergo the late adult pipeline before being terminated. This is vital for the study of human age-related diseases and allows us to identify late-onset phenotypes.
All of the data generated by the phenotyping centres is sent to the Data Coordination Centre (DDC) at MRC Harwell where it undergoes validation, QC checks and statistical analysis. The DDC sends the preliminary data to the Core Data Archive at EMBL-EBI where it undergoes further statistical analysis and is finalised into released data. Queen Mary’s University London performs disease association analysis at this stage. The release data and disease associations are loaded onto our online open-access database where it is available for all users.
Read more in our paper on High-throughput mouse phenomics, Nature Reviews Genetics 2018