Transgenic Animals Unit 3, Chapter 3

What is a transgenic animal? A species that carries one or more genes form another species. Continued to improve since the 1970’s Are important tools for biomedical research May be the answer to the shortage of human organs for transplant Scientist have been able to mask markers on pig organs so human system will not reject Helping to set the stage for gene therapy

Introduction Biotechnology: Is a collection of scientific techniques that use living cells and molecules to make products and solve problems. By using natural processes of living organisms (animals, plants and bacteria), biotechnology allows us to enhance our health, our environment and our food supply.

The Past: These are not new ideas! For thousands of years, selective breeding has been used to improve livestock, control plant pollination and to produce better crops Microorganisms have been used to bake bread, brew beer and make cheese! Today, some of the same microorganisms are used to produce human hormones (like insulin for diabetics) and to improve our livestock and crops.

Creating a Transgenic Organism Transgenic organisms are created by transferring specific genes from one species to another. The first transgenic organisms were bacteria Transgenic bacteria are still used today by pharmaceutical companies to produce a variety of human proteins such as insulin, human growth hormone and interferons (a family of substances with antiviral and anticancer abilities.

Benefits of Transgenic Organisms Models of human disease A way to improve the quality and health of livestock Another method to produce pharmaceuticals A source of organs for humans A model for gene therapy in humans (substituting the normal gene for hemoglobin to replace the one that causes sickle cell anemia)

First Transgenic Animal In 1975, scientist implanted an ape gene into a mouse. The mouse produced the ape protein but did not pass the gene onto offspring. Two years later, the same researchers produced the first transgenic mouse strain, whose offspring did contain the implanted transgene.

The Harvard Mouse Transgenic animal production increased rapidly in the 1980’s as scientists improved genetic engineering techniques and identified and purified more genes. In 1988, Dr. Philip Leder and Timothy Stewart introduced the Harvard Mouse, a strain that carries the human oncogene that predisposes mice to cancer. This was the first U.S. patent for a genetically engineered animal. This mouse strain and many others remain commercially available today.

Benefits of Transgenic Animals 1. To use as Animal models: Mice are more often used for research for several reasons: *They reproduce quickly *They are small animals and are housed easily. *Their genetic makeup is better understood than other mammals *Their lifespan is two to three years, allowing researchers to follow disease processes from infancy to old age over a relatively short time.

Benefits of Transgenic Animals 2. Pharmaceutical production: For decades, bacteria has served as “factories” for many products such as insulin and hormones. Scientist can now use transgenic animals to produce these substances, known as “pharming”, this is an economical alternative.

Benefits: Introducing the gene into a large farm animal has many advantages: *It is reproducible *The amount of drug produced is limited only by the number of successful transgenic animals produced and its offspring. *Maintaining the animal is more economical compared to the amount of drug produced, than growing cells in tissue culture.

Benefits: 3. Organ donors: There is a desperate shortage of organs to be transplanted into ill patients. Scientists are studying an alternative using organs from other species, called “xenografts”. They are working on ways that will reduce rejection of the organ Scientist are working with pigs to see if their organs can be used successfully.

Benefits: There are advantages to using pigs for organ transplants: *They carry few viruses or other infectious agents that could be transferred to the organ recipient. They reproduce quickly and have large litters There is less social opposition to using pigs than to using non-human primates. Scientist have created ways to make pig organs look more “human” to resist rejection.

Benefits: 4. Livestock improvement: *Creating animals that are larger, leaner, use feed more efficiently and are more resistant to disease. Very expensive Some consumers are against eating products from transgenic animals

How to Produce a Transgenic Animal 1. Construct the transgene, which is the DNA to be transferred. 2. Inject the gene into a single cell embryo. The following method is used to produce transgenic mice: 1. Female mice are given hormones so they superovulate (produce a large number of eggs) 2. They are mated

Producing Transgenic Animals 3. Hours later, single-cell embryos are removed from the females 4. Using a microscope and a microinjector, scientists inject each embryo with copies of the transgene 5. These eggs are then transferred to surrogate mothers of the same strain that have been treated with hormones so the eggs can implant and grow.

Producing a Transgenic Animal Scientist can determine if the mice in the litter have the gene by analyzing a small piece of each mouse’s tail when it is 8 to 10 days old, using a technique called polymerise chain reaction or PCR. Millions of copies of a gene can be made in a few hours This has been used to study DNA from a 40,000 year old frozen woolly mammoth!

Producing a Transgenic Animal The success rate of introducing transgenes into embryos is low. Example: 100 mouse embryos are microinjected. 60% survive and are reimplanted into surrogate mother mice 30% of these (or 18 embryos) implant and are born 10%-30% of the 18 mouse pups born should be transgenic The larger the animal, the success rate decreases.

Care of Transgenic Animals Scientist only use the healthiest animals and do their best to keep the animals healthy . As a protective measure, scientists sometimes incorporate a special start signal (promoter region) with the gene so that the gene is expressed in a specific tissue or organ. Researchers are constantly testing observing their animals for any unexpected effects of the genes they introduce.

Governments Role in Transgenic Animals Controversy developed after the U.S. Patent and Trademark office granted Harvard University a patent on their oncomouse in 1988 Animal rights activists filed an unsuccessful suit against the patent office, claiming that the government did not have the right to patent life forms Congress failed 3 times to enact a moratorium against patenting animals

Governments Role: The NIH, National Institute of Health uses transgenic animals in biomedical research The U.S. Department of Agriculture (USDA) uses them in livestock and veterinary research The only policy specifically addressing the use of genetically altered animals is the NIH Guidelines for research Involving recombinant DNA Molecules

Ethical Considerations People are concerned about the possibilityu that animals and plants with altered genetic characteristics could threaten our environment, our health and our food supply. Animal welfare groups feel that genetic manipulation will lead to increased animal suffering Others believe that scientist are playing “GOD” Some people believe that scientist will one day use these techniques on humans

Ethical Considerations This concern surfaced in February 1997 when researchers in Scotland announce that they had successfully cloned an adult sheep, producing Dolly, a younger, genetically identical “twin” or the original.

Benefits of Transgenic Animals 1. Transgenic animal models provide a powerful new way to study numerous diseases 2. Vital substances needed by the human body may soon be available at a reasonable cost. 3. Sufficient numbers of human organs are not available for transplantation and transgenic animals may provide a new source of organs

Benefits: 4. Transgenic techniques may one day be used to treat human diseases such as sickle cell anemia and cancer The Future of Transgenic Animals: The use of transgenic models have become an established part of biomedical research. May lead the way to gene therapy in humans that may provide treatments and possible cures for many diseases.