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PLoS Genet. 2014 Oct 23;10(10):e1004705. doi: 10.1371/journal.pgen.1004705. eCollection 2014 Oct.

Identification of genes important for cutaneous function revealed by a large scale reverse genetic screen in the mouse.

Author information

1
Department of Biochemistry and Molecular Biology, Monash University, Clayton, Melbourne, Australia.
2
Wellcome Trust Sanger Institute, Genome Campus, Hinxton, Cambridge, United Kingdom.
3
Centre for Stem Cells and Regenerative Medicine King's College London, Guy's Hospital, London, United Kingdom.
4
Wellcome Trust Sanger Institute, Genome Campus, Hinxton, Cambridge, United Kingdom; Wolfson Centre for Age-Related Diseases, King's College London, Guy's Campus, London, United Kingdom.
5
The Jackson Laboratory, Bar Harbor, Maine, United States of America.
6
Department of Biochemistry and Molecular Biology, Monash University, Clayton, Melbourne, Australia; Department of Anatomy and Developmental Biology, Monash University, Clayton, Melbourne, Australia.

Abstract

The skin is a highly regenerative organ which plays critical roles in protecting the body and sensing its environment. Consequently, morbidity and mortality associated with skin defects represent a significant health issue. To identify genes important in skin development and homeostasis, we have applied a high throughput, multi-parameter phenotype screen to the conditional targeted mutant mice generated by the Wellcome Trust Sanger Institute's Mouse Genetics Project (Sanger-MGP). A total of 562 different mouse lines were subjected to a variety of tests assessing cutaneous expression, macroscopic clinical disease, histological change, hair follicle cycling, and aberrant marker expression. Cutaneous lesions were associated with mutations in 23 different genes. Many of these were not previously associated with skin disease in the organ (Mysm1, Vangl1, Trpc4ap, Nom1, Sparc, Farp2, and Prkab1), while others were ascribed new cutaneous functions on the basis of the screening approach (Krt76, Lrig1, Myo5a, Nsun2, and Nf1). The integration of these skin specific screening protocols into the Sanger-MGP primary phenotyping pipelines marks the largest reported reverse genetic screen undertaken in any organ and defines approaches to maximise the productivity of future projects of this nature, while flagging genes for further characterisation.

PMID:
25340873
PMCID:
PMC4207618
DOI:
10.1371/journal.pgen.1004705
[Indexed for MEDLINE]
Free PMC Article

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