MadSci Network: Genetics

Growing Human Organs Using Mouse DNA

Area: Genetics
Posted By: David Miller, MD/PhD Student, Neuroscience
Date: Fri Sep 20 10:18:45 1996
Message ID: 842143445.Ge

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 

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 

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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