Creating Giant Mice Through Gene Regulation

In 1982, a group of molecular geneticists led by Richard Palmiter at the University of Washington produced gigantic mice that grew to almost twice the size of normal mice. Palmiter and his colleagues created these large mice through genetic engineering, by injecting the rat gene for growth hormone into the nuclei of fertilized mouse embryos and then implanting these embryos into surrogate mouse mothers. In a few embryos, the rat gene became incorporated into the mouse chromosome and, after birth, these trans-

genic mice produced growth hormone encoded by the rat gene. Some of the transgenic mice produced from 100 to 800 times the amount of growth hormone found in normal mice, which caused them to grow rapidly into giants.

Inserting foreign genes into bacteria, plants, mice, and even humans is now a routine procedure for molecular geneticists (see Chapter 18). However, simply putting a gene into a cell does not guarantee that the gene will be transcribed or produce a protein; indeed, most foreign genes are never transcribed or translated, which isn't surprising. Organisms have evolved complex systems to ensure that genes are expressed at the appropriate time and in the appropriate amounts, and sequences other than the gene itself are required to ensure transcription and translation. In this chapter, we will learn more about these sequences and other mechanisms that control gene expression.

If foreign genes are rarely expressed, why did the trans-genic mice with the gene for rat growth hormone grow so big? Palmiter and his colleagues, aware of the need to provide sequences that control gene expression, linked the rat gene with the mouse metallothionein I promoter sequence, a DNA sequence normally found upstream of the mouse metallothionein I gene. When heavy metals such as zinc are present, they activate the metallothionein promoter sequence, thereby stimulating transcription of the metal-lothionein I gene. By connecting the rat growth-hormone gene to this promoter, Palmiter and his colleagues provided a means of turning on the transcription of the gene, simply by putting extra zinc in the food for the transgenic mice.

This chapter is about gene regulation, the mechanisms and systems that control the expression of genes. We begin by discussing why gene regulation is necessary; the levels at which gene expression is controlled; and the difference between genes and regulatory elements. We then examine gene regulation in bacterial cells. In the second half of the chapter, we turn to gene regulation in eukaryotic cells, which is often more complex than in bacterial cells.

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