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

作者：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; Watt Fiona M^*

来源：Nature Communications, 2014, 5(1): 3540.

DOI：10.1038/ncomms4540

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.

• 出版日期2014-4