Beneath the skin
Researchers report the first comprehensive analysis of genes that affect a single tissue. Genes don’t act in isolation and it is only by studying the effects of many genes that scientists can gain a more accurate and holistic view of the complex biology of tissues.
The team found 50 genes that affect development of skin in the mouse, including nine already known to play a role in human disease. Around half of the genes that affect skin were not active in skin, but in other tissues, showing how important it can be to take an approach to discovery that is unbiased by preconceptions of which genes might affect function in which tissue.
The team inactivated genes in the mouse and looked for consequences on normal body function and disease: the focus of this study was on skin.
“This is one of the first studies to look at one organ at this scale, with samples from over 530 genes. Such a large-scale study allows us to look at genes that might not otherwise have been thought to be associated with skin development.
“We have not focused on those genes whose biology suggests they might be implicated in normal skin function or in disease of the skin. Rather, we have taken an objective, evidence-based approach to uncover genes whose role in skin development was not known.”
Dr Ramiro Ramirez-Solis Head of Mouse Pipelines at the Wellcome Trust Sanger Institute
The team looked at 530 genes: remarkably, mutations in one in eleven had an effect on skin development. The team were able to detect effects on skin that ranged from changes to fur or paw colour, to the arrangement of the individual hair follicles, to the flakiness of the skin.
“We found nine genes that we knew already are associated with human diseases that have a skin component, and these mouse models could be a new means of studying the diseases or finding treatments. We also found new mutations that could help us to understand skin conditions that affect patients and perhaps help to develop new diagnostics.”
Professor Fiona Watt Director of the Centre for Stem Cells and Regenerative Medicine, King’s College London
To validate the screening approach, the team looked in detail at three genes whose mutations are known to be involved in human disease. In one case, mutation in a gene called Myo5A causes effects in the mouse that mimic Griscelli syndrome. The team also found effects for mutations in a related gene, Myo7a, suggesting that this, also, might play a role in human skin disease.
In one case, skin development in mutant mice was influenced by diet: mice fed on a high-fat diet showed less effect of the mutation than those on normal feed.
“Surprisingly, some of the 50 genes that cause skin conditions in the mouse are not active in skin tissue. These will be important in understanding human disease and would probably not be found without such a large-scale project.
“This study shows the value of unbiased examination of as many genes as possible, rather than selecting only those thought to be involved in skin development or maintenance.”
Professor Karen Steel from the Wolfson Centre for Age-Related Diseases, King’s College London and the Sanger Institute
Such a large array of newly identified genes should improve our understanding of human skin biology and improve clinical care. All of the information and resources generated are freely available so that other scientists can easily follow up on these new discoveries.
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The Wolfson Centre for Age-Related Diseases
The Wolfson Centre for Age-Related Diseases is a state of the art research facility that was opened in 2004 to develop strategies aimed at restoring function to the damaged nervous system. Our research is led by one of the most vibrant groupings of neuroscientists at King’s College London. We have 25 principle investigators (PIs), and a total of over 120 staff, including ~ 50 PhD students. We use our collective expertise to evaluate and develop new therapies for pain, spinal cord injury and degenerative diseases. In the last RAE approximately 80% of our research was rated as world leading/internationally excellent.
The Centre for Stem Cells and Regenerative Medicine
The Centre for Stem Cells and Regenerative Medicine, King’s College London is led by Professor Fiona Watt. Researchers in the Centre are particularly interested in how stem cells interact with their local environment, or niche. An understanding of these interactions is important for developing effective cell therapies in the clinic. Located on the Guy’s Hospital campus, the Centre acts as a focus for cutting-edge stem cell research taking place across the College and its partner NHS Trusts, as part of King’s Health Partners.
King's College London
King’s College London is one of the top 20 universities in the world (2013/14 QS World University Rankings), and the fourth oldest in England. A research-led university based in the heart of London, King’s has nearly 23,500 students (of whom more than 9,000 are graduate students) from nearly 140 countries, and some 6,000 employees. King’s is in the second phase of a £1 billion redevelopment programme which is transforming its estate.
King’s has an outstanding reputation for providing world-class teaching and cutting-edge research. In the 2008 Research Assessment Exercise for British universities, 23 departments were ranked in the top quartile of British universities; over half of our academic staff work in departments that are in the top 10 per cent in the UK in their field and can thus be classed as world leading. The College is in the top seven UK universities for research earnings and has an overall annual income of nearly £450 million.
King’s has a particularly distinguished reputation in the humanities, law, the sciences (including a wide range of health areas such as psychiatry, medicine, nursing and dentistry) and social sciences including international affairs. It has played a major role in many of the advances that have shaped modern life, such as the discovery of the structure of DNA and research that led to the development of radio, television, mobile phones and radar.
King’s College London and Guy’s and St Thomas’, King’s College Hospital and South London and Maudsley NHS Foundation Trusts are part of King’s Health Partners. King’s Health Partners Academic Health Sciences Centre (AHSC) is a pioneering global collaboration between one of the world’s leading research-led universities and three of London’s most successful NHS Foundation Trusts, including leading teaching hospitals and comprehensive mental health services. For more information, visit:
The Wellcome Trust Sanger Institute
The Wellcome Trust Sanger Institute is one of the world’s leading genome centres. Through its ability to conduct research at scale, it is able to engage in bold and long-term exploratory projects that are designed to influence and empower medical science globally. Institute research findings, generated through its own research programmes and through its leading role in international consortia, are being used to develop new diagnostics and treatments for human disease.
The Wellcome Trust
The Wellcome Trust is a global charitable foundation dedicated to achieving extraordinary improvements in human and animal health. We support the brightest minds in biomedical research and the medical humanities. Our breadth of support includes public engagement, education and the application of research to improve health. We are independent of both political and commercial interests.
