Novel skin phenotypes revealed by a genome-wide mouse reverse genetic screen
Novel skin phenotypes revealed by a genome-wide mouse reverse genetic screen
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.
Animals, Databases, Genetic, Female, Humans, Male, Mice, Mice, Knockout, Mutation, Phenotype, Reverse Genetics/methods, Skin
Liakath-Ali, Kifayathullah
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Vancollie, Valerie E.
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Heath, Emma
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Smedley, Damian P.
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Estabel, Jeanne
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Sunter, David
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DiTommaso, Tia
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White, Jacqueline K.
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Ramirez-Solis, Ramiro
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Smyth, Ian
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Steel, Karen P.
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Watt, Fiona M.
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11 April 2014
Liakath-Ali, Kifayathullah
8d5a020c-e976-4901-9195-68f4bc0de74e
Vancollie, Valerie E.
f5178931-9739-4c6d-80d7-eb5945d7226b
Heath, Emma
1d342be5-7208-4589-9134-5f3e79649297
Smedley, Damian P.
6d482007-a5a8-4096-a75c-874505306fec
Estabel, Jeanne
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Sunter, David
c94cae6f-e144-46d4-9b63-3891a9e44b8b
DiTommaso, Tia
d4ac7f2d-660b-42df-9f7d-06313d499015
White, Jacqueline K.
2fc3e1cd-d296-475d-9552-b476729a7f69
Ramirez-Solis, Ramiro
6dbe5c4a-6a38-4abb-9c53-d3a2db827d98
Smyth, Ian
60e61aea-3b71-4bce-a6ad-f2bfe5972f6f
Steel, Karen P.
5ed72b90-2400-41b4-a0ed-0bc8c4b60315
Watt, Fiona M.
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Liakath-Ali, Kifayathullah, Vancollie, Valerie E., Heath, Emma, Smedley, Damian P., Estabel, Jeanne, Sunter, David, DiTommaso, Tia, White, Jacqueline K., Ramirez-Solis, Ramiro, Smyth, Ian, Steel, Karen P. and Watt, Fiona M.
(2014)
Novel skin phenotypes revealed by a genome-wide mouse reverse genetic screen.
Nature Communications, 5, [3540].
(doi:10.1038/ncomms4540).
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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ncomms4540
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Accepted/In Press date: 4 March 2014
Published date: 11 April 2014
Keywords:
Animals, Databases, Genetic, Female, Humans, Male, Mice, Mice, Knockout, Mutation, Phenotype, Reverse Genetics/methods, Skin
Identifiers
Local EPrints ID: 491451
URI: http://eprints.soton.ac.uk/id/eprint/491451
ISSN: 2041-1723
PURE UUID: 8fd315c9-380f-4d46-a029-044be255ca0d
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Date deposited: 24 Jun 2024 16:49
Last modified: 25 Jun 2024 02:10
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Contributors
Author:
Kifayathullah Liakath-Ali
Author:
Valerie E. Vancollie
Author:
Emma Heath
Author:
Damian P. Smedley
Author:
Jeanne Estabel
Author:
David Sunter
Author:
Tia DiTommaso
Author:
Jacqueline K. White
Author:
Ramiro Ramirez-Solis
Author:
Ian Smyth
Author:
Karen P. Steel
Author:
Fiona M. Watt
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