Chapter 7: Animal Biotechnology Introduction to Biotechnology Fall 2006

B1 B4 B2 B3

What are some of the animals… Mice Rats Zebrafish (3 month generation time, 200 progeny, complete embryogenesis in 120 hrs) Dogs (lungs and cardiovascular system) Cats Pigs (PPL Therapeutics- delete a gene which causes hyperacute rejection of pig-to-human organ transplantation) Primates (HIV and AIDs research, geriatric research)

Alternatives to Animal Models (figure 7.5) Cell culture devices Researchers use cell cultures and computer- generated models whenever possible, but this doesn’t work for looking at an organ or entire animal

Regulation of Animal Research The “Three Rs” Reduce the number of higher species (cats, dogs, primates) used Replace animals with alternative models whenever possible Refine tests and experiments to ensure the most humane conditions possible

Veterinary Medicine as Clinical Trials Treatments for humans may also be useful for treatments with animals (e.g. the BRCA1 gene found in 65% of human breast tumors is similar to the BRCA1 gene in dogs) Hypthermia + radiation = more effective at killing tumors Stimulation of cytokines for curing skin cancers

Bioengineering Mosquitoes to Prevent Malaria Cloned in a gene that prevents the parasite from traversing the midgut; blocking the continuation of its life cycle Developed an antibody that prevents the parasite from entering the mosquito’s salivary gland

Clones Creating Dolly Start with Embryo Twinning (splitting embryos in half) Cloning (figure 7.7) Limits to Cloning: The donor cell must come from a living organism An organism is also shaped by its environment The success rate for cloning is very low Clones may be old before their time The future of cloning: preservation of endangered animals, studying the effect of drugs etc on duplicates, improve agricultural production

Transgenic Animals Retrovirus-mediated transgenesis Pronuclear microinjection (figure 7.8) Embronyic stem cell method Sperm-mediated transfer

Improving Agricultural Products with Transgenics Faster growth rates or leaner growth patterns (improve the product), more product Increase nutritional content-lactoferrin Turning the animals into efficient grazers Transfer antimicrobial genes to farm animals

Transgenic Animals as Bioreactors Biosteel otherwise known as spider silk, cloned into goat milk (“silkmilk” goats) Goats reproduce faster than cows and are cheaper than cows Hens also make good bioreactors in that they are cheap and a lot of eggs are produced at one time

Knock-outs: A Special Case of Transgenesis A specific gene is disrupted or removed such that it is not expressed (Figure 7.11) Procedure: DNA is modified, it is added to embryonic stem cells, where it undergoes homologous recombination. The modified ES cells are then introduced into normal embryo. The embryo is implanted in an incubator mother. The offspring is a chimera. It may take several generations of crossbreeding are required to produce animals that are complete knock-outs. Breast cancer mouse

Producing Human Antibodies in Animals 1980’s Concept of the “magic bullet” Figure 7.12: Production of Mabs  Used to treat cancer, heart disease, and transplant rejection  HUMANIZED monoclonal antibodies were developed to prevent the human anti- mouse antibody (HAMA) response