|MadSci Network: Genetics|
Dear Jason, I enjoyed reading your question on the molecular genetics of transplantation. There are really two areas of transplantation that you touched on. The first is the issue of making cells that have DNA from both mice and humans. This kind of a combination is called a chimera. The way this is done is to insert the human DNA (alias "the gene") into a retrovirus. A retrovirus can infect (actually this is called 'transfection') the mouse cells and insert the human DNA/gene into the mouse genome (a genome is all the DNA of an animal). If it works, the mouse cells will express a human gene which essentially is a "nametag" that says "I'm a human cell". This nametag is actually called HLA for Human Leukocyte Antigen. The utility of this approach is in bone marrow transplants. People who have leukemia (a disease of white blood cells) sometimes receive bone marrow transplants in an attempt to provide a source of healthy white blood cells. New white blood cells are formed in the bone marrow, thus the reason for bone marrow transplantation. Theoretically, mouse white blood cells that express the human "nametag" gene will not be rejected when transplanted into a human. Normally, mouse cells injected into a human would be killed off immediately because they have the wrong "nametag". This technique could potentially be a very good way of producing a lot of bone marrow cells to transplant into humans. The second issue involves transplantation of whole organs. This cannot reasonably be done from mice because they're just too darn small. Pigs, however, have organs that are a lot closer to the size of the ones we have and thus represent the best option for providing organs which can be donated to humans. The pigs, like the mice, are also made to express a human gene. When the pigs reach adult size, their organs can be used for transplantation into humans. The "nametag" genes that the pig organs express are DAF for Decay Accelerating Factor, and the human blood group antigens (the ABO antigens). DAF is a molecule involved in the blood clotting pathway and is also involved in organ rejection. The ABO antigens are used to distinguish a person's blood type. Type A blood cells have the "A" molecule, type B has the "B" molecule, type AB has both and type O has neither. Early results indicate that expression of human DAF and ABO antigens by the transplanted organ significantly reduces the severity of the rejection response of the organ's recipient. You should know that all of these procedures, to my knowledge, are currently experimental. There are no guarantees yet that these molecular genetic solutions to transplantation will work. Currently, patients in need of transplants rely entirely on people who are generous enough to donate. I'm not sure what your library resources are like, but here are a couple articles to get you started... 1. Nature (a science journal) Volume 377, page 185. This article is about using pigs for transplantation and includes a nice pig picture. 2. Immunology Today (another journal) Volume 16 Number 11, page 529. This is an article about using the human-mouse chimeras, but is pretty technical. It does have diagrams, however.
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