Bloomsbury report on mouse embryo phenotyping: recommendations from the IMPC workshop on embryonic lethal screening

Abstract

Identifying genes that are important for embryo development is a crucial first step towards understanding their many functions in driving the ordered growth, differentiation and organogenesis of embryos. It can also shed light on the origins of developmental disease and congenital abnormalities. Current international efforts to examine gene function in the mouse provide a unique opportunity to pinpoint genes that are involved in embryogenesis, owing to the emergence of embryonic lethal knockout mutants. Through internationally coordinated efforts, the International Knockout Mouse Consortium (IKMC) has generated a public resource of mouse knockout strains and, in April 2012, the International Mouse Phenotyping Consortium (IMPC), supported by the EU InfraCoMP programme, convened a workshop to discuss developing a phenotyping pipeline for the investigation of embryonic lethal knockout lines. This workshop brought together over 100 scientists, from 13 countries, who are working in the academic and commercial research sectors, including experts and opinion leaders in the fields of embryology, animal imaging, data capture, quality control and annotation, high-throughput mouse production, phenotyping, and reporter gene analysis. This article summarises the outcome of the workshop, including (1) the vital scientific importance of phenotyping embryonic lethal mouse strains for basic and translational research; (2) a common framework to harmonise international efforts within this context; (3) the types of phenotyping that are likely to be most appropriate for systematic use, with a focus on 3D embryo imaging; (4) the importance of centralising data in a standardised form to facilitate data mining; and (5) the development of online tools to allow open access to and dissemination of the phenotyping data.

Three-dimensional correction of conduction velocity in the embryonic heart using integrated optical mapping and optical coherence tomography

“…35,44 The knockout mouse phenotyping project (KOMP) has already found ∼10% of transgenic mice have CHDs. 45 It is likely that a large proportion of these defective hearts have conduction abnormalities. Yet, these hearts have not been assayed for conduction defects.…”

Mouse Models of Syndromic Craniosynostosis

“…Conventional techniques generating mouse models with recombination technology has been slow and expensive, and the use of genome editing technologies could overcome these issues. This could be particularly useful in systematic phenotypic screens for mouse embryos [Adams et al, 2013]. There is an international effort to delineate the phenotypes of knockout mice generated from the International Knockout Mouse Consortium (IKMC).…”

“…The International Mouse Phenotyping Consortium (IMPC) (http://www.mousephenotype. org/), as it became known, aims to phenotypically screen 20,000 knockouts in 10 years [Adams et al, 2013]. The importance of screening phenotypes allows the corroboration between genotype to phenotype and especially in the case of embryonic lethal models that helps to pinpoint critical pathways for development.…”

Leveraging Online Resources to Prioritize Candidate Genes for Functional Analyses: Using the Fetal Testis as a Test Case

“…At least 30% of the targeted knockouts generated in mouse by programs such as the IKMC and IMPC result in embryonic or perinatal death [Adams et al, 2013]. This lead to the inception of the Wellcome Trust-funded research program Deciphering the Mechanisms of Developmental Disorders (DMDD; https://dmdd.org.uk; [Mohun et al, 2013; Adams et al, 2013; Wilson et al, 2016]) that aims to characterize these lethal mutants further.…”