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


Type
Article
Change log
Authors
DiTommaso, Tia 
Jones, Lynelle K 
Cottle, Denny L 
WTSI Mouse Genetics Program 
Gerdin, Anna-Karin 
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.

Description
Keywords
Animals, Embryonic Stem Cells, Hair Follicle, Mice, Mutation, Phenotype, Reverse Genetics, Skin Physiological Phenomena
Journal Title
PLoS Genet
Conference Name
Journal ISSN
1553-7390
1553-7404
Volume Title
10
Publisher
Public Library of Science (PLoS)