Biomedical Engineering Reference
In-Depth Information
biomedical science, from genetics to cell biology, neurobiology to cancer
biology, and immunology to developmental biology.
So, what makes us so sure we can extrapolate from studies in mice
any information that is applicable to humans? There are several reasons.
First, the number of nucleotides in rodents and humans, and indeed in
all mammalian species, is roughly the same, about 3 billion bp. Second,
the number of genes in these species is the same, and by and large (with
only a few exceptions) there is a 1:1 relationship between a gene in a
human and in the mouse. Thus, for any given gene in the human genome
there is a counterpart with a similar if not identical function in the mouse.
Third, and more remarkably, the location and linkages of genes on the
chromosomes is very similar. Thus, by mapping a disease susceptibility
gene in the mouse, investigators already may have insights into where
to search, and what to search for, in humans. True, mouse and human
genes differ in nucleotide sequence, with an average difference of 20%
to 30% per gene, but some are very conserved.
In this section, some of the methods used to alter the genetic makeup
of mice, by both breeding and experimental manipulation, will be pre-
sented.
B.
Inbred strains of mice
At the beginning of the century, scientists were attempting to de-
velop ways to study the characteristics of tumors. They could readily
identify cancers that would spontaneously develop in experimental an-
imals, but because tissue culture techniques had not been developed,
there was no way to propagate these cells in vitro. As an alternative ap-
proach, investigators attempted to passage (transfer) these tumors from
one experimental animal to another, but they invariably failed to grow.
Today we understand that these tumors were rejected by the immune
response of the recipient animal against the histocompatibility antigens
expressed on the tumor, much like transplanted organs between two
unrelated persons are rejected.
A breakthrough in the ability to study tumors occurred when scien-
tists used transplanted tumors that spontaneously arose within closed
colonies of mice. These were mice that had been bred for certain rare
characteristics. In the and early centuries, the collecting
of mice with unusual features was a popular hobby, and mouse fanciers
around the world were always on the lookout for such mice. Two of
the most collectable mice were albino mice (which are white and have
pink eyes due to lack of pigmentation) and “Japanese Waltzing” mice.
Japanese Waltzing mice could not stand up straight, but would turn in
circles, and lose their balance. This characteristic is now known to be
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