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Chapter 7 Animal Biotechnology Animals in Research Animals in Research B1 B2 B3 B4 Animals in Research FDA Oversight of Drug Development Process • Pre-Clinical Research and Development Animation: Drug Development Process Animals in Research FDA Oversight of Drug Development Process • Pre-Clinical Animal Studies Animals in Research Animal Models • 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) Animals in Research Alternatives to Animal Models • 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 Animals in Research 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 Animals in Research 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) • Hyperthermia + radiation = more effective at killing tumors • Stimulation of cytokines for curing skin cancers Animals in Research 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 Cloning A genetically identical copy of a cell or whole organism Cloning Embryogenesis – the process by which the embryo forms and develops • Zygote – fertilized egg • Blastocyst – early stage embryo prior to implantation Cloning Methods Embryo Twinning Embryo Twinning Animation Cloning Methods Somatic Cell Nuclear Transfer Cloning Methods A look at Dolly the Sheep Cloning Methods Somatic Cell Nuclear Transfer SCNT Animation Cloning Methods Click and Clone a Mouse Limits to Cloning Decrease Genetic Diversity Limits to Cloning Epigenetic Effects Limits to Cloning Efficiency and Cost Effectiveness Limits to Cloning Abnormal Development Limits to Cloning Premature Aging Telomerase Animation The Future of Cloning Increase in genetic gain The Future of Cloning Consistent Quality The Future of Cloning Endangered Species Transgenic Animals Transgenic Animal – genome has been changed to carry genes from a different species Transgenic Techniques Embryonic Stem Cell Method Transgenic Techniques Pronuclear Injection Animation of Pronuclear Injection Transgenic Techniques Making clones of a transgenic animal Animation: Using SCNT to make transgenic goat Transgenic Applications Increased Production Efficiency: Transgenic Growth Hormones Transgenic Applications Improved Food Safety and Quality: longer shelf life Transgenic Applications Improved Food Safety and Quality: lactose intolerance Transgenic Applications Increase Nutritional Content: Lactoferrin Transgenic Applications Increased Production Efficiency: boost lactational performance Transgenic Applications Disease Resistant Animals less susceptible to mastitis Transgenic Applications Disease Resistant Animals less susceptible to mad cow disease Transgenic Applications Decreased Environmental Impact Transgenic 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 Transgenic Animals Knock-outs: A Special Case of Transgenesis • A specific gene is disrupted or removed such that it is not expressed • 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 Production of Monoclonal antibodies (Mabs) • • Used to treat cancer, heart disease, and transplant rejection HUMANIZED monoclonal antibodies were developed to prevent the human antimouse antibody (HAMA) response