Geneticists engineer a new mouse: Laboratory animals give research scientists 'tailor-made models of human disease'

UNDERSTANDING one of the principal causes of kidney disease in children will be easier following the creation of a new strain of laboratory mouse by genetic engineering, scientists said yesterday.

The animal is the latest in a series of 'knock-out' mice that have had non-functional genes inserted into them when embryos, to mimic the symptoms of human genetic disorders ranging from cystic fibrosis and sickle-cell anaemia to cancer.

Researchers at the Whitehead Institute in Cambridge, Massachusetts, have beaten British scientists in the race to knock out the gene shown to be linked with Wilms' tumour, the primary cause of kidney cancer in children and responsible for about 6 per cent of all childhood cancers.

The gene in question is known as a tumour suppressor. Tumours occur when the gene is damaged by mutation, so preventing it from functioning normally. When children inherit a non-functional copy of the gene from one parent and a functional copy from the other, they are at risk of developing kidney cancer.

'Cancer develops in these children when some event disrupts the one normal copy of the gene in a single kidney cell; as a result, the cell grows out of control, producing a tumour,' the Whitehead Institute said.

The new strain of mouse, described in the current issue of the journal Cell, carries a functional and a non-functional copy of the gene, just like the children at risk.

Such mice are normal, but when they mate with each other some of their offspring inherit two non-functional copies of the Wilms' tumour gene and die at the embryo stage because they fail to develop kidneys.

According to Rudolf Jaenisch, head of the Whitehead research team, this proved that the gene plays a key role in the early development of kidneys. 'They will allow us to begin sorting out at the molecular level the complex interactions that must occur to produce normal kidneys.'

There are now several hundred different strains of knock-out mice, according to Professor Nick Hastie, a geneticist at the Medical Research Council's Human Genetics Unit in Edinburgh. They are proving invaluable in studying human diseases where there is no equivalent condition in the animal world, he said.

Mice that have had a gene for an important brain enzyme knocked out, for instance, cannot remember how to escape from a maze, helping scientists to understand the physical basis of learning. Other knock-out mice lacking a gene for a brain protein are helping researchers to understand the genetics of 'mad cow' disease and Creutzfeldt-Jakob disease in humans.

Kenneth Paigen, director of the Jackson Laboratory in Bar Harbor, Maine - which has done much of the work in identifying natural strains of laboratory mouse - says in the current issue of the journal Nature that knock-out mice represent a scientific revolution: 'We suddenly have the ability to create tailor-made mammalian models of human disease which offers the opportunity to study complex physiological phenomena, such as the nervous and immune systems, Aids and cancer, as never before.'

Not everyone, however, is so happy about 'playing God' by creating artificial strains of laboratory animals. Animal rights activists in Europe have opposed attempts to patent a strain of mouse that has been genetically programmed to die of cancer after a few months, arguing that such research is unethical because it increases the suffering of animals.

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