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Genes 2014, 5(4), 887-925; doi:10.3390/genes5040887

Mouse ENU Mutagenesis to Understand Immunity to Infection: Methods, Selected Examples, and Perspectives

1
Department of Human Genetics, McGill University, Montréal, QC H3G 0B1, Canada
2
Complex Traits Group, McGill University, Montréal, QC H3G 0B1, Canada
3
Department of Medicine, McGill University, Montréal, QC, H3G 0B1, Canada
4
Department of Biochemistry, McGill University, Montréal, QC, H3G 0B1, Canada
5
McGill University and Genome Quebec Innovation Center, Montréal, QC, H3A 1A4, Canada
6
McGill Life Sciences Complex, Bellini Building, 3649 Sir William Osler Promenade, Room 367, Montreal, QC, H3G 0B1, Canada
These authors contributed equally to this work.
*
Author to whom correspondence should be addressed.
Received: 27 June 2014 / Revised: 19 August 2014 / Accepted: 21 August 2014 / Published: 29 September 2014
(This article belongs to the Special Issue Grand Celebration: 10th Anniversary of the Human Genome Project)
View Full-Text   |   Download PDF [3470 KB, uploaded 29 September 2014]   |  

Abstract

Infectious diseases are responsible for over 25% of deaths globally, but many more individuals are exposed to deadly pathogens. The outcome of infection results from a set of diverse factors including pathogen virulence factors, the environment, and the genetic make-up of the host. The completion of the human reference genome sequence in 2004 along with technological advances have tremendously accelerated and renovated the tools to study the genetic etiology of infectious diseases in humans and its best characterized mammalian model, the mouse. Advancements in mouse genomic resources have accelerated genome-wide functional approaches, such as gene-driven and phenotype-driven mutagenesis, bringing to the fore the use of mouse models that reproduce accurately many aspects of the pathogenesis of human infectious diseases. Treatment with the mutagen N-ethyl-N-nitrosourea (ENU) has become the most popular phenotype-driven approach. Our team and others have employed mouse ENU mutagenesis to identify host genes that directly impact susceptibility to pathogens of global significance. In this review, we first describe the strategies and tools used in mouse genetics to understand immunity to infection with special emphasis on chemical mutagenesis of the mouse germ-line together with current strategies to efficiently identify functional mutations using next generation sequencing. Then, we highlight illustrative examples of genes, proteins, and cellular signatures that have been revealed by ENU screens and have been shown to be involved in susceptibility or resistance to infectious diseases caused by parasites, bacteria, and viruses. View Full-Text
Keywords: infectious diseases; ENU; immunity; mouse genetic models infectious diseases; ENU; immunity; mouse genetic models
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

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MDPI and ACS Style

Caignard, G.; Eva, M.M.; van Bruggen, R.; Eveleigh, R.; Bourque, G.; Malo, D.; Gros, P.; Vidal, S.M. Mouse ENU Mutagenesis to Understand Immunity to Infection: Methods, Selected Examples, and Perspectives. Genes 2014, 5, 887-925.

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