The use of animals in the MRC
Both extramural and intramural research funded by the MRC involves the use of animals. The majority of the procedures undertaken intramurally by MRC-funded units and institutes involve the breeding of genetically modified animals (57% in 2011). This might be to discover the function of a particular gene thought to be involved in the causation of disease. Animals are also used in fundamental research to try to find out more about what keeps humans and animals alive and healthy. It is important to understand exactly how the different tissues and organs of the body work when healthy, and to find out what goes wrong when disease strikes. Much is done to understand the properties of neuronal networks in the brain and how they underlie behaviour in normal conditions and in models of neurological disorders (such as Parkinson’s disease).
The vast majority of the animals used by the MRC are rodents, and predominantly mice. This is because mice are widely considered to be the prime model of human disease. They share 99% of their genes with humans and 90% of the genes associated with disease are identical in human and mouse. More than 95% of the mouse genome has also been sequenced, and as a result of mouse-human genome comparisons, around 1200 new genes have been discovered in the human, a significant number of which are likely to be involved in cancers and other diseases (The Measure Of Man, Sanger Institute Press Release, 5 December 2002).
The zebrafish is also a common animal used by the MRC. The zebrafish is important in studying developmental origins of health and disease as their embryos are transparent and develop outside the body, allowing simple study of the developing embryo. The use of the zebrafish in research is also advancing knowledge in a wide range of other areas, including tissue regeneration and cancer. Zebrafish exhibit a rare ability to repair their own tissue, including the spinal cord, retina, and heart, which it is hoped could lead to the development of new treatments that will one day allow the human heart to heal itself. Even if they lose up to 20% of a ventricle, the animals form a clot that stops bleeding within seconds and then gradually replace the lost tissue. Within a month or so, they are back to normal.
Zebrafish also develop tumours with a remarkable likeness to human ones, and so might be useful for screening anti-cancer drugs.
Other animals used include ferrets, rabbits, the laboratory opossum, frogs, and macaques.
Zebrafish mending hearts |
The zebrafish, which can mend its own heart muscle, is providing clues to heart failure. Heart failure affects 750,000 people in the UK. This condition of the heart muscle, often caused by a heart attack, is a leading cause of disability. Zebrafish are important in biomedical science because they are semi-transparent and have a fully functioning simple heart and circulatory system. If part of their heart is removed, they can grow it back in a matter of weeks. Researchers recently identified a molecule that tells certain stem cells in the zebrafish embryo whether to become either heart muscle or blood vessel cells. This molecule – called Fibroblast growth factor (Fgf) – may be the evolutionary switch that triggered four-chambered human hearts, from the two-chambered ‘tube’ in fish. The hope is that the Fgf switch can prompt stem cells to create brand new heart muscle in people with heart defects or who have suffered a heart attack. In the lab, the research will help the production of stem cells for use in heart repair. |
Mice and sex development disorders |
Abnormalities in human sexual development are relatively common, occurring in approximately 1 in 250 newborns. Those with the 46 XY disorder of sex development (DSD) exhibit a range of symptoms, such as germ cell tumours, ambiguous genitalia, and infertility. A definitive diagnosis of the genetic cause of 46 XY DSDs is hampered by the lack of understanding of how, and which, genes control testis determination. Researchers are studying the developmental process by which the mammalian embryo becomes either male or female – sex determination. Using mouse genetics, scientists have identified a defective gene (MAP2K1) expressed in the developing gonads at the time when the decision to develop as a testis or ovary is made. This gene is now routinely screened in individuals with 46 XY DSD to offer a potential diagnosis of their birth defect. |
Early-onset hearing loss |
Deafness can occur early in life with around 1 in 1000 children affected, which can result in delayed development of speech, language and cognitive skills, and may result in slow learning and difficulty progressing in school. More than 70% of hereditary hearing loss is nonsyndromic (no associated visible abnormalities of the external ear or any related medical problems). To date, ~130 areas of chromosome (loci) that cause non-syndromic hearing impairment have been mapped in the human genome, although the genes underlying ~50% of these loci have not been identified. Currently, we are far from determining a complete picture of the genetic networks underlying the auditory system. Researchers at MRC Harwell continue to make a very significant impact upon the discovery of deafness models in the mouse. Studies have identified causative genes involved in the ionic composition of the inner ear and a cell-signalling mechanism. Further studies will identify the precise cause of the hearing deficit and indicate the specific role of these genes in the auditory system. |
Statistics of animal use within the MRC
The number of procedures carried out by researchers in MRC units and institutes reported to the Home Office in 2011 was 421,296. These were carried out on 420,296 animals. This is 11% of the total procedures reported to the Home Office for that year. Of the 421,296 procedures, 95% were on mice, 4% on fish and <1% on macaques.
Breeding of Genetically Modified (GM) or Harmful Mutant (HM) animals accounted for 57% of all procedures carried out. The number of procedures undertaken on animals covered by special protection legislation were as follows:
- Macaques: 69
- Cats: 0
- Dogs: 0
- Horses: 0