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Nat Commun. 2014 Apr 11;5:3540. doi: 10.1038/ncomms4540.

Novel skin phenotypes revealed by a genome-wide mouse reverse genetic screen.

Author information

1
1] Centre for Stem Cells and Regenerative Medicine, King's College London, Guy's Hospital, London SE1 9RT, UK [2] Department of Biochemistry, University of Cambridge, Tennis Court Road, Cambridge CB2 1QW, UK [3] Wellcome Trust-Medical Research Council Stem Cell Institute, University of Cambridge, Tennis Court Road, Cambridge CB2 1QR, UK.
2
Wellcome Trust Sanger Institute, Genome Campus, Hinxton, Cambridge CB10 1SA, UK.
3
Centre for Stem Cells and Regenerative Medicine, King's College London, Guy's Hospital, London SE1 9RT, UK.
4
1] Department of Anatomy and Developmental Biology, Monash University, Wellington Road, Clayton, Victoria 3800, Australia [2] Present address: Brigham Regenerative Medicine Center, Brigham and Women's Hospital, Boston, Massachusetts 02115, USA.
5
Department of Anatomy and Developmental Biology, Monash University, Wellington Road, Clayton, Victoria 3800, Australia.
6
1] Wellcome Trust Sanger Institute, Genome Campus, Hinxton, Cambridge CB10 1SA, UK [2] Wolfson Centre for Age-Related Diseases, King's College London, Guy's Campus, London SE1 1UL, UK.

Abstract

Permanent stop-and-shop large-scale mouse mutant resources provide an excellent platform to decipher tissue phenogenomics. Here we analyse skin from 538 knockout mouse mutants generated by the Sanger Institute Mouse Genetics Project. We optimize immunolabelling of tail epidermal wholemounts to allow systematic annotation of hair follicle, sebaceous gland and interfollicular epidermal abnormalities using ontology terms from the Mammalian Phenotype Ontology. Of the 50 mutants with an epidermal phenotype, 9 map to human genetic conditions with skin abnormalities. Some mutant genes are expressed in the skin, whereas others are not, indicating systemic effects. One phenotype is affected by diet and several are incompletely penetrant. In-depth analysis of three mutants, Krt76, Myo5a (a model of human Griscelli syndrome) and Mysm1, provides validation of the screen. Our study is the first large-scale genome-wide tissue phenotype screen from the International Knockout Mouse Consortium and provides an open access resource for the scientific community.

PMID:
24721909
PMCID:
PMC3996542
DOI:
10.1038/ncomms4540
[Indexed for MEDLINE]
Free PMC Article

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