In the news
6 Sep 2008
27 July 2007
3 new projects launched to replace GM mice
The Dr Hadwen Trust is funding ground-breaking research to target non-animal replacements in the world’s fastest growing area of animal use – genetic experiments.
Recent years have seen a rapid rise in the number of genetically modified (GM) animals used in experiments. Over 950,000 procedures were conducted on transgenic animals in the UK alone in 2005, representing one third of all procedures. An additional 288,000 procedures were conducted on animals with a harmful genetic defect and analysis of Home Office statistics reveals there has been an 1884% increase in GM animal experiments since 1990.
The research community urgently need to addresses this upward trend with a replacement focus. Therefore the Dr Hadwen Trust has identified the replacement of transgenic animals as a key strategic priority. We are funding pioneering research at top UK universities to target this work.
Says Nicky Gordon, Dr Hadwen Trust:
“GM mouse research can cause substantial suffering to animals and researchers are increasingly encountering incidents where human genes and mouse genes, have unexpectedly different functions1 . That has significant implications for the usefulness of animal ‘models’ of human diseases and it is vital that a more reliable, human-relevant method is developed.”
3-D human tissue structures with targeted gene disruptions:
We are funding researchers at the University of York to develop methods to silence genes in human tissues grown in the laboratory, to replace the use of knockout mice. These ‘knockout tissues’ will be created from a type of adult stem cell called mesenchymal stem cells (MSC), taken from donated bone marrow. The work could have important applications in the study of arthritis and bone disease.
Says Dr Paul Genever, the lead researcher on the project:
“Knockout mice are frequently used to try to determine the potential function of a particular gene(s). Significantly, it is unclear how accurately the data obtained from knockout models translates to human physiology. This new work will, for the first time, identify the potential for using MSC to generate “knockout tissues”. If successful, this work will have far-reaching implications for cost and efficiency of biological research, our understanding of gene function and will contribute significantly to the replacement of mouse knockout experiments.”
Human tissue model for premature birth research:
Our collaborative research at King’s College, London and Manchester University is focusing on the genes involved in the control of labour. Abnormal labour, such as premature labour, affects some 30% of all pregnancies in the UK. Babies born at 23 weeks have just a 17% chance of survival but relatively little is known about how the human womb works. Much research has relied on animal experiments but important differences in the physiology of human pregnancy and that of other animals mean that results have had little impact on our understanding of human pregnancy.
Our researchers will use strips of human uterus tissue, donated by pregnant women who have undergone caesarean section, to construct a test tube model. Uterus tissue maintains the ability to contract in the test tube for at least four days. The latest molecular biology tools will be used to silence the genes of interest, and understand their role in the control of contractions. No similar test tube model is known to currently exist.
Says Dr Rachel Tribe, joint principal research:
“In general, there is an over-reliance on the use of transgenic animals for studying genes in human biology. For researchers concerned with understanding human labour, there are inherent problems with this approach as mice do not represent a good model. It is imperative that we develop a non-animal replacement technique for silencing gene and protein expression in human uterine tissue as a more scientifically appropriate alternative to using transgenic animals.”
3D model of skin cancer:
We are also funding leading cancer researchers at the Centre for Cutaneous Research at Queen Mary’s School of Medicine and Dentistry, London, to develop the world’s first multi-cellular model of a type of skin cancer called Basal cell carcinoma (BCC). BCC is responsible for three-quarters of all skin cancers in the West and is the most common form of human cancer. Tumours usually occur on the face and neck, which are difficult areas to treat and require complicated surgery that can leave unsightly scarring. If caught early, BCC can be treated, but otherwise it can become dangerous.
At present there are no cell culture models of BCC and research is often carried out on mice genetically modified to develop tumours. Sometimes human skin cells may be implanted into mice with deficient immune systems in an attempt to model the disease. A single experiment can use as many as 400 mice; tumours can be large, aggressive and painful.
Says Professor Mike Philpott, Professor of Cutaneous Biology & lead researcher:
“Currently basal cell carcinoma is modelled using animals but by developing this three-dimensional model, we intend to generate a viable alternative. Also because our model will include genetically modified human cells we hope to demonstrate the flexibility of our model as a system to investigate basic biology underlying the development of skin cancer. Ultimately we would hope that this research into a new model system would also drive further development of three-dimensional models of other skin cancers.”
ENDS
1 Odom, D.T. et al (2007) Tissue-specific transcriptional regulation has diverged significantly between human and mouse. Nature Genetics, 39(6):730-32
