Novel gene function revealed by mouse mutagenesis screens for models of age-related disease

Paul K. Potter, Michael R. Bowl, Prashanthini Jeyarajan, Laura Wisby, Andrew Blease, Michelle E. Goldsworthy, Michelle M. Simon, Simon Greenaway, Vincent Michel, Alun Barnard, Carlos Aguilar, Thomas Agnew, Gareth Banks, Andrew Blake, Lauren Chessum, Joanne Dorning, Sara Falcone, Laurence Goosey, Shelley Harris, Andy Haynes, Ines Heise, Rosie Hillier, Tertius Hough, Angela Hoslin, Marie Hutchison, Ruairidh King, Saumya Kumar, Heena V. Lad, Gemma Law, Robert E. MacLaren, Susan Morse, Thomas Nicol, Andrew Parker, Karen Pickford, Siddharth Sethi, Becky Starbuck, Femke Stelma, Michael Cheeseman, Sally H. Cross, Russell G. Foster, Ian J. Jackson, Stuart N. Peirson, Rajesh V. Thakker, Tonia Vincent, Cheryl Scudamore, Sara Wells, Aziz El-Amraoui, Christine Petit, Abraham Acevedo-Arozena, Patrick M. Nolan, Roger Cox, Anne-Marie Mallon and Steve D. M. Brown ()
Additional contact information
Paul K. Potter: MRC Harwell Institute, Mammalian Genetics Unit, Harwell Campus
Michael R. Bowl: MRC Harwell Institute, Mammalian Genetics Unit, Harwell Campus
Prashanthini Jeyarajan: MRC Harwell Institute, Mammalian Genetics Unit, Harwell Campus
Laura Wisby: MRC Harwell Institute, Mammalian Genetics Unit, Harwell Campus
Andrew Blease: MRC Harwell Institute, Mammalian Genetics Unit, Harwell Campus
Michelle E. Goldsworthy: MRC Harwell Institute, Mammalian Genetics Unit, Harwell Campus
Michelle M. Simon: MRC Harwell Institute, Mammalian Genetics Unit, Harwell Campus
Simon Greenaway: MRC Harwell Institute, Mammalian Genetics Unit, Harwell Campus
Vincent Michel: Génétique et Physiologie de l'Audition, Institut Pasteur, INSERM UMR-S 1120, Sorbonne Universités, UPMC Univ Paris 06, Collège de France
Alun Barnard: The Nuffield Laboratory of Ophthalmology & NIHR Oxford Biomedical Research Centre, University of Oxford
Carlos Aguilar: MRC Harwell Institute, Mammalian Genetics Unit, Harwell Campus
Thomas Agnew: MRC Harwell Institute, Mammalian Genetics Unit, Harwell Campus
Gareth Banks: MRC Harwell Institute, Mammalian Genetics Unit, Harwell Campus
Andrew Blake: MRC Harwell Institute, Mammalian Genetics Unit, Harwell Campus
Lauren Chessum: MRC Harwell Institute, Mammalian Genetics Unit, Harwell Campus
Joanne Dorning: MRC Harwell Institute, Mammalian Genetics Unit, Harwell Campus
Sara Falcone: MRC Harwell Institute, Mammalian Genetics Unit, Harwell Campus
Laurence Goosey: MRC Harwell Institute, Mammalian Genetics Unit, Harwell Campus
Shelley Harris: MRC Harwell Institute, Mammalian Genetics Unit, Harwell Campus
Andy Haynes: MRC Harwell Institute, Mammalian Genetics Unit, Harwell Campus
Ines Heise: MRC Harwell Institute, Mammalian Genetics Unit, Harwell Campus
Rosie Hillier: MRC Harwell Institute, Mammalian Genetics Unit, Harwell Campus
Tertius Hough: MRC Harwell Institute, Mammalian Genetics Unit, Harwell Campus
Angela Hoslin: MRC Harwell Institute, Mammalian Genetics Unit, Harwell Campus
Marie Hutchison: MRC Harwell Institute, Mammalian Genetics Unit, Harwell Campus
Ruairidh King: MRC Harwell Institute, Mammalian Genetics Unit, Harwell Campus
Saumya Kumar: MRC Harwell Institute, Mammalian Genetics Unit, Harwell Campus
Heena V. Lad: MRC Harwell Institute, Mammalian Genetics Unit, Harwell Campus
Gemma Law: MRC Harwell Institute, Mammalian Genetics Unit, Harwell Campus
Robert E. MacLaren: The Nuffield Laboratory of Ophthalmology & NIHR Oxford Biomedical Research Centre, University of Oxford
Susan Morse: MRC Harwell Institute, Mammalian Genetics Unit, Harwell Campus
Thomas Nicol: MRC Harwell Institute, Mammalian Genetics Unit, Harwell Campus
Andrew Parker: MRC Harwell Institute, Mammalian Genetics Unit, Harwell Campus
Karen Pickford: MRC Harwell Institute, Mammalian Genetics Unit, Harwell Campus
Siddharth Sethi: MRC Harwell Institute, Mammalian Genetics Unit, Harwell Campus
Becky Starbuck: MRC Harwell Institute, Mammalian Genetics Unit, Harwell Campus
Femke Stelma: MRC Harwell Institute, Mammalian Genetics Unit, Harwell Campus
Michael Cheeseman: The Roslin Institute and Royal (Dick) School of Veterinary Studies, University of Edinburgh
Sally H. Cross: MRC Human Genetics Unit, Institute of Genetics and Molecular Medicine, University of Edinburgh, Western General Hospital
Russell G. Foster: John Radcliffe Hospital, University of Oxford
Ian J. Jackson: The Roslin Institute and Royal (Dick) School of Veterinary Studies, University of Edinburgh
Stuart N. Peirson: John Radcliffe Hospital, University of Oxford
Rajesh V. Thakker: Oxford Centre for Diabetes, Endocrinology and Metabolism, University of Oxford, Churchill Hospital
Tonia Vincent: Kennedy Institute of Rheumatology, Rheumatology and Musculoskeletal Sciences, University of Oxford
Cheryl Scudamore: MRC Harwell Institute, Mammalian Genetics Unit, Harwell Campus
Sara Wells: MRC Harwell Institute, Mammalian Genetics Unit, Harwell Campus
Aziz El-Amraoui: Génétique et Physiologie de l'Audition, Institut Pasteur, INSERM UMR-S 1120, Sorbonne Universités, UPMC Univ Paris 06, Collège de France
Christine Petit: Génétique et Physiologie de l'Audition, Institut Pasteur, INSERM UMR-S 1120, Sorbonne Universités, UPMC Univ Paris 06, Collège de France
Abraham Acevedo-Arozena: MRC Harwell Institute, Mammalian Genetics Unit, Harwell Campus
Patrick M. Nolan: MRC Harwell Institute, Mammalian Genetics Unit, Harwell Campus
Roger Cox: MRC Harwell Institute, Mammalian Genetics Unit, Harwell Campus
Anne-Marie Mallon: MRC Harwell Institute, Mammalian Genetics Unit, Harwell Campus
Steve D. M. Brown: MRC Harwell Institute, Mammalian Genetics Unit, Harwell Campus

Nature Communications, 2016, vol. 7, issue 1, 1-13

Abstract: Abstract Determining the genetic bases of age-related disease remains a major challenge requiring a spectrum of approaches from human and clinical genetics to the utilization of model organism studies. Here we report a large-scale genetic screen in mice employing a phenotype-driven discovery platform to identify mutations resulting in age-related disease, both late-onset and progressive. We have utilized N-ethyl-N-nitrosourea mutagenesis to generate pedigrees of mutagenized mice that were subject to recurrent screens for mutant phenotypes as the mice aged. In total, we identify 105 distinct mutant lines from 157 pedigrees analysed, out of which 27 are late-onset phenotypes across a range of physiological systems. Using whole-genome sequencing we uncover the underlying genes for 44 of these mutant phenotypes, including 12 late-onset phenotypes. These genes reveal a number of novel pathways involved with age-related disease. We illustrate our findings by the recovery and characterization of a novel mouse model of age-related hearing loss.

Date: 2016
References: Add references at CitEc
Citations: View citations in EconPapers (1)

Downloads: (external link)
https://www.nature.com/articles/ncomms12444 Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:7:y:2016:i:1:d:10.1038_ncomms12444

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/ncomms12444

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().