Science: Why mice, not dogs, are man's best friend
Over 3,000 genes in mice are closely related to those in human beings
Friday 04 June 1999
And what is that key? Mice. When Burns wrote of the schemes of mice and men he could not have imagined how important that relationship would become. As the director of the American National Institutes of Health put it: "We recognise the incredible importance of the mouse for a wide array of biological and medical problems."
But what is a laboratory with more than 900 scientists and support staff and hundreds of thousands of mice doing on a beautiful island, isolated from any academic institution? Its origins can be traced to 1909 when a Harvard undergraduate, Clarence Cook Little, was puzzled about why some mouse tumours could be transplanted to another animal and continue to grow, while others could not.
He realised that in order to study the problem it was necessary to have inbred mice whose genetic constitution did not vary. He started to inbreed mice in his apartment, keeping them in the bath. He got the mice from mouse-fanciers; among them were mice from Japan.
Little became president of the University of Maine and then of the University of Michigan, but continued his interest in biology and took students on field trips to Maine in the summer. When he left his post at Michigan in 1929, he founded the laboratory, to study cancer using mice.
The advantages of mice include their small size and rapid breeding cycle - females start breeding at six to eight weeks and gestation time is just three weeks. Mice get most of the diseases of human beings, including diabetes, high blood pressure, atherosclerosis, glaucoma, epilepsy and cancer. All of these are influenced by genes and mutations can both directly cause the diseases and predispose the organism to them. Understanding the genetics of these conditions would be extremely difficult in human populations but, fortunately, the genes in the mouse are similar to our own - large portions are almost identical. The mapping and sequencing of mouse genes is doing well and should be completed at about the same time as that of the human genome. Over 3,000 genes have been identified in mice that are closely related to those in human beings, and the number of such genes is increasing almost daily.
The mission of the laboratory is to identify the genes that may contribute to these diseases. The standard way of finding mutations is to keep a lookout for deviant mice in the colony, those with a different coat colour or a limp, or some other abnormal behaviour. About 20 such mice are carefully examined each week. In this way genes associated with seizures that resemble epilepsy have been found. Two major genes causing glaucoma have been identified, but this required development of new techniques for measuring pressure within the eye.
There are also new technologies for manipulating the genes that enable the researcher to create a mouse with a particular gene inactivated or modified. This technique is based on the ability to culture cells from the early embryo that retain their capacity to give rise to any of the mouse's organs when introduced back into a developing embryo. These cells are the ones in which the gene is modified, and they are then introduced into an early embryo. There is even a company that will, for a not insignificant price, supply cells with any particular gene inactivated. This technology can also be used to make the mouse's immune system more like our own and so help to study Aids in the mouse. All these mice are for sale - at reasonable prices - to other workers; more than 2,000 different ones are on offer.
The amount of information being collected, both at the Jackson and worldwide, is monumental. In order to deal with it all the laboratory has created a database in which every relevant mouse paper appearing in a scientific journal is carefully entered, and it already contains more than 50,000 entries.
Much as I love dogs, it may be that mice will turn out to be man's and woman's best friend.
The writer is professor of biology as applied to medicine at University College London
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