19 May 2014
By Valerie E Vancollie
Screen strategy. On receipt, tail skin was divided into three parts: one was processed for epidermal wholemount immunostaining, one for paraffin conventional histology and one for genomic DNA extraction. Credit: doi:10.1038/ncomms4540
The screening of over 500 genes in the mouse has led us to the discovery of genes
newly identified as being involved in skin abnormalities, including some that affect humans such as inflammatory hair disorders and Griscelli syndrome. Identifying the genes linked to these often severe conditions is a first step towards developing treatments.
With the advent of large-scale knock-out programmes like the Mouse Genetics Project (MGP) at the Wellcome Trust Sanger Institute, which knocks out or deletes individual genes in mice in order to identify their function, similar large-scale, tissue-specific screens have become possible. One such screen was performed in collaboration with Fiona Watt, Kifayahullah Liakath-Ali and Emma Heath from the Wattlab at King’s College London, who specialise in skin-related research.
During the course of the collaboration, we sent them an average of two tails from each mutant mouse line produced for the MGP, collected after the mice had died. They studied the tail epidermis, which were stained with fluorescent chemicals that detect keratin proteins K14 and K15 and a stain called DAPI that highlights cell nuclei. The staining helped the researchers to study various components of the skin such as the hair follicles, sebaceous glands and interfollicular epidermal tissue. Using these tail samples allowed for a greater study of the skin than was possible with live mice.
Different versions of 538 genes were examined over the course of the project and 50 mutants were found to have a skin condition, ranging from abnormal pigmentation and flaky skin to abnormal sebaceous glands and disrupted hair follicle patterning. Of these, nine are linked with a human disorder such as Griscelli syndrome, and three of these (Krt76, Myo5a and Mysm1) were studied in greater depth. These mouse lines could now be used to further our understanding of the skin abnormalities of those disorders and, hopefully, pave the way to finding drugs or cures to treat them.
All of the phenotyping data, and mutant images generated as part of this collaboration are freely available to the scientific community and the mutant mice can be obtained from specific mouse archives in Europe and the USA. All of this allows for further research to be performed on any of the abnormalities discovered during the study.
Valerie E Vancollie is an advanced research assistant phenotyper on the Mouse Genetics Project Phenotyping Team at the Wellcome Trust Sanger Institute.
- Liakath-Ali K et al. (2014) Novel skin phenotypes revealed by a genome-wide mouse reverse genetic screen. Nature Communications. doi:10.1038/ncomms4540
- White JKet al. (2013) Genome-wide generation and systematic phenotyping of knockout mice reveals new roles for many genes.Cell. doi:10.1016/j.cell.2013.06.022