Since the mid-1970s, due to the development of genetic engineering technology, people have gradually realized the desire to introduce foreign genes into mammalian cells. For example, someone successfully introduced herpes tk and human β globin genes into mouse teratoma cells. Others obtained chimeric mice by introducing mouse teratoma cells into the embryo cavity of early mouse embryos. 1980, scientists from Yale University introduced recombinant plasmids containing two kinds of viral DNA into the pronucleus of mouse fertilized eggs by microinjection, and cultivated offspring mice with this foreign DNA sequence. Encouraged by these studies, scientists at the University of Washington introduced the rat growth hormone gene into the fertilized eggs of mice, and obtained a mouse whose genome was integrated with the rat growth hormone gene, which was two to three times heavier than that of ordinary mice. This is 1982, a "super mouse" published in the American magazine Nature. "Super Mouse" became the focus of news media reports for a while, and some famous scientists wrote articles praising the revolutionary significance of "Super Mouse" in biology.

"Super mouse" is the beginning of the transgenic animals we are talking about today. It is a "new animal" containing specific foreign genes by introducing specific foreign genes into early embryonic cells of animals and integrating them into their genomes, and then passing them on to future generations through germ cell lines. Transgenic animal system breaks the interspecific isolation under natural conditions and enables genes to flow between distant organisms; Some new protein with economic value can be produced through the expression of transgenic animals. Compared with prokaryotic expression system, the produced protein can maintain its natural biological activity. In particular, the mammary gland is used as a bioreactor, so that a large amount of synthesized protein is secreted into the milk, and the products can be collected without harming individual animals, so that mass production can be carried out at a low price. In addition, transgenic animals can effectively avoid unfavorable genes and transfer favorable traits to high-yield lines, thus reducing the manpower, financial resources and time required for backcrossing. In recent years, some experimental animal models produced by transgenic technology provide convenience for basic theoretical research and medical practice.

Since the birth of "super mouse", it has had a global impact on the whole life science. Therefore, it was recognized as the fourth generation technology after genetic relay chromosome linkage analysis (early 20th century), somatic genetics (1960s) and gene recombination technology (1970s) at the first international gene mapping conference199/kloc-0, and it was listed in the history of biological development.

Transgenic animals are animals that have stably integrated specific DNA fragments of foreign genes in their genomes through experimental methods. Therefore, in theory, any animal can be made into corresponding transgenic animals through sex line gene manipulation, such as transgenic sheep, transgenic chickens, transgenic fish, transgenic birds, etc., but most of them are mammalian transgenic animals at present. According to the different ways of gene introduction, transgenic animals can be roughly divided into three types: random insertion type, homologous recombination gene knockout type and homologous recombination gene substitution type. Random insertion refers to the insertion of foreign genes into the genome of animals; Homologous recombination gene knockout means that an important part of animal genes is replaced by homologous recombination of genes, thus destroying genes; Homologous recombination gene replacement is to use homologous recombination of genes to replace defective genes in animals with normal genes, thus restoring the function of genes.

The rise of transgenic animal technology can not only provide animal models for scientific research, but also provide various medicinal proteins for human beings, which has high economic value. 199065438+In February, a Dutch pharmaceutical company bred the world's first transgenic cow by means of transgenic animals. Its milk contains human lactoferrin. This kind of protein is a natural organic iron, which is easily absorbed by human body, and is very needed by pregnant women, infants and patients with iron deficiency anemia. The estimated annual output value of milk powder made from the milk produced by this genetically modified cow can reach about 5 billion US dollars. 199 1 year, an American pharmaceutical company successfully produced α- 1 antitrypsin (α 1-at, which can treat cystic fibrosis) from transgenic sheep. The highest expression level of α- 1-at can reach 60 grams per liter of goat milk. Another team of British scientists transferred the gene of trypsin (which can be used to treat emphysema and other diseases) into goats. One goat can produce trypsin worth $7 a day, which is much higher than the output and lower cost of trypsin extracted from animal pancreas at present. Transgenic goats bred by Vulka Institute in Tel Aviv contain 10g human serum albumin per liter of goat milk, and each goat can provide 10kg protein every year. Scientists in Finland have transferred human erythropoietin into a heifer, and it is estimated that it can produce 137 pounds of drugs in its milk every year. Scientists in China have studied genetic animals since 1985, and have obtained transgenic mice and sheep of human growth hormone, interferon and hepatitis B virus. The adoption of transgenic animal technology provides basic conditions for the industrialization of transgenic drugs and genetic engineering breeding of livestock.

In addition, in recent years, scientists also imagine that transgenic animal technology can be used to transform animal organs, so that organs transplanted into human bodies do not produce or less immune rejection, which is undoubtedly another gospel of human health. Among many animals, pig's organs are closest to human organs in shape, size and function. Therefore, scientists decided to start with genetically modified pigs. A research team from Cambridge University, England, is ahead of others in this respect, and has bred transgenic pigs with human-specific genes in their hearts, which can prevent the rejection of heart transplantation. It is conceivable that if the heart, kidney and liver of transgenic pigs can be produced on a large scale for organ transplantation, it will be a great boon to mankind.

The research on transgenic animals is only 10 years, and its achievements have attracted worldwide attention. How to improve the integrated expression rate of transgene, realize gene transfer and discover new transgenic genes is a problem that scientists need to solve. With the continuous improvement of transgenic technology and the maturity of gene targeting technology, transgenic animals will study by going up one flight of stairs to better benefit mankind.