The International Mouse Phenotyping Consortium: past and future perspectives on mouse phenotyping

Abstract

Determining the function of all mammalian genes remains a major challenge for the biomedical science community in the 21st century. The goal of the International Mouse Phenotyping Consortium (IMPC) over the next 10 years is to undertake broad-based phenotyping of 20,000 mouse genes, providing an unprecedented insight into mammalian gene function. This short article explores the drivers for large-scale mouse phenotyping and provides an overview of the aims and processes involved in IMPC mouse production and phenotyping.

Fig. 1

Organisation of the International Mouse Phenotyping Consortium. A core of mouse production and phenotyping centres is allied to the data centre supporting IMPC. The mouse production/ phenotyping centres will also network with a variety of biomedical research centres that will undertake more specialised phenotyping on selected lines and provide additional expertise and input into the IMPC phenotyping programme

Fig. 2

Design of the knockout first, conditional-ready allele employed by IMPC. The tm1a allele (that itself provides a knockout through splicing into the lacZ reporter) is generated in ES cells. Mice generated with the tm1a allele are crossed to an appropriate Cre driver to eliminate both a key exon within the gene and remove the selection cassette, generating the tm1b null allele. The tm1b allele will be phenotyped by IMPC. Alternatively, Flp action on the tm1a allele can produce the tm1c conditional-ready allele (adapted from Skarnes et al. 2011)

Fig. 3

The adult IMPC phenotyping pipeline. The diagram illustrates the pipeline of in-life tests from 9 to 15 weeks, as well as the terminal tests carried out subsequently at 16 weeks

Fig. 4

Biological systems explored through the adult IMPC phenotyping pipeline. All of the tests in the IMPC phenotyping pipeline are grouped according to the systems they explore

Fig. 5

Embryonic phenotyping pipeline. A possible triage strategy for embryonic phenotyping is illustrated. Homozygotes are generated from heterozygote intercrosses and are assessed first at E12.5 for viability. If viable, gross morphology and 3D imaging can be undertaken and lacZ reporter expression determined. Subsequently, E15.5 embryos can be assessed. If embryos are not viable at E12.5, then E9.5 embryos are assessed