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

Kifayathullah Liakath-Ali; Valerie E Vancollie; Emma Heath; Damian P Smedley; Jeanne Estabel; David Sunter; Tia Ditommaso; Jacqueline K White; Ramiro Ramirez-Solis; Ian Smyth; Karen P Steel; Fiona M Watt

doi:10.1038/ncomms4540

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

Kifayathullah Liakath-Ali, Valerie E Vancollie, Emma Heath, Damian P Smedley, Jeanne Estabel, David Sunter, Tia Ditommaso, Jacqueline K White, Ramiro Ramirez-Solis, Ian Smyth, Karen P Steel, Fiona M Watt

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.
Wellcome Sanger Institute
King's College London
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.
Monash University

Research output: Contribution to journal › Article › peer-review

44 Citations (Scopus)

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.

Original language	English
Article number	3540
Pages (from-to)	N/A
Number of pages	13
Journal	Nature Communications
Volume	5
Issue number	N/A
DOIs	https://doi.org/10.1038/ncomms4540
Publication status	Published - 11 Apr 2014

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title = "Novel skin phenotypes revealed by a genome-wide mouse reverse genetic screen",

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.",

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AU - Liakath-Ali, Kifayathullah

AU - Vancollie, Valerie E

AU - Heath, Emma

AU - Smedley, Damian P

AU - Estabel, Jeanne

AU - Sunter, David

AU - Ditommaso, Tia

AU - White, Jacqueline K

AU - Ramirez-Solis, Ramiro

AU - Smyth, Ian

AU - Steel, Karen P

AU - Watt, Fiona M

PY - 2014/4/11

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

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