The Transgenic Mouse

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In 1982, the creation of the first "transgenic animal" was accomplished by transferring a gene from one animal to the embryo of another--a mouse--in such a way that the gene would be expressed in the mouse and in its future offspring. The transgenic technology was developed by Richard Palmiter of the UW Department of Biochemistry in collaboration with Ralph Brinster of the University of Pennsylvania. First in the world to accomplish this feat, the researchers were honored with the Charles Leopold Mayer prize in 1994, the highest honor bestowed by the French Academy of Sciences.footnote 1

Palmiter and Brinster implanted a foreign gene into fertilized mouse eggs, transferred the eggs to surrogate mother mice, and then documented that the gene functioned in several of the offspring. By breeding these offspring, they further demonstrated that the gene could be passed on from generation to generation.

Scientists working with transgenic techniques believe that the work will shed light on how information in our genetic "blueprint" is uncoded in living organisms, and how genes are switched on and work in the normal course of development as well as in disease states. They see the creation of the transgenic mouse as a major step forward in the search for genetic therapies to treat disorders caused by errors in the genetic code.

Palmiter and Brinster set out to understand how cells read the genetic code and translate that information into biological structures. The techniques they used are based on the fact that genes have two main parts: regions that code for particular proteins, and regulatory regions that tell genes when to activate. An on-off control region can be hooked up with a foreign gene from another organism and still exert its effect. Palmiter and Brinster had been working with the on-switch, or promoter, for the protein metallothionein (MT), which binds the metal ions of copper, zinc, and cadmium. They took the MT promoter and attached it to an unrelated gene, one which codes for an easily measured enzyme (thymidine kinase). They placed the composite, "designer" gene into freshly fertilized mouse eggs and found that cadmium, which normally turns on the MT gene, now turned on the thymidine kinase gene in the mouse eggs.

The researchers followed a similar strategy to couple the MT promoter with the rat growth hormone gene and to transfer that composite gene to mice, which resulted in "supermice" of larger than normal size. The results were published in 1982 in the journal Nature.

The transgenic mice have provided Palmiter and Brinster a way to test experimental models and treatments for diseases. In one instance, the researchers have given the mice genes that lead to faulty livers. They then implanted healthy mouse liver cells, which grew into new, healthy liver tissue. Mouse models of other diseases, including cancer, sickle cell disease, and diabetes, also have been studied. While genetically engineered treatments for human diseases remain far off at this point, the work of Palmiter and Brinster has brought the world closer to realizing that dream.

  1. Kathleen Klein, Columns, December 1995.

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