Biomedical Engineering Reference
In-Depth Information
the recessive allele. Although it is time consuming and expensive, the
value of this approach is that it can be used to target, in theory, every
gene in the body. In addition, the generation of point mutations often
results in phenotypes that are different from those that are revealed
in gene deletion in knockout mice, since protein products are usually
made carrying the mutations. This can make it more difficult for other
gene products to compensate for the affected gene.
Bone marrow chimeras
Bone marrow chimeras, also known as radiation chimeras or tetra-
parental mice, are mice that have had all of their hematopoietic cells
replaced using bone marrow stem cells from other mice. This is a com-
mon tool that is used in immunologic studies. Recipient mice are lethally
irradiated (hence the name “radiation” chimera), which destroys all of the
progenitor cells in the bone marrow, including pleuripotent stem cells.
They are then reconstituted with bone marrow cells from donor animals,
which survive indefinitely, as well as give rise to committed progenitor
cells that differentiate to form all of the blood elements, including erythro-
cytes (red blood cells), lymphocytes, monocytes, neutrophils, platelets,
etc. These mice will then be permanently reconstituted with the blood
cells from another animal. Consequently, they are referred to as “tetra-
parental” (yes, four parents.) chimeras.
Adoptive transfer
Adoptive transfer is a method in which immune cells (lymphocytes)
from one mouse are used to provide immunity to an antigen or pathogen
to another mouse. To perform an adoptive transfer experiment, recipient
mice are sublethally irradiated (350R to 450R versus the lethal dose of
irradiation required to totally eliminate stem cells from the bone marrow,
which ranges from 850R to 1100R). Sublethal irradiation temporarily de-
pletes lymphocytes from secondary lymphoid organs (spleen and lymph
nodes), which provides room for the cells to be transferred. In contrast
to the production of bone marrow chimeras, in an adoptive transfer ex-
periment mature cells, usually lymphocytes and often from an immune
donor, are transferred into recipient mice. Because these cells have lim-
ited lifespan and do not (normally) repopulate themselves, the chimeric
state that is achieved in adoptive transfer experiments is short-lived.
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