Biomedical Engineering Reference
In-Depth Information
are mated with a host strain of mice that can be distinguished on
the basis of a large number of easily defined genetic polymorphisms.
Frequently, differences called simple sequence length polymorphisms
(SSLPs) are used for this purpose, since these can be identified
rapidly by PCR. SSLPs are, as the name implies, differences in the
number of base pairs of DNA found between two homologous re-
gions between two different individuals. Because the genome of higher
organisms has far more DNA than is required to code for the nec-
essary genes, segments of DNA can be added, or subtracted, from
noncoding regions without having any deleterious effect, giving rise to
SSLPs.
In producing speed congenics, mice are screened after the first
backcross generation for both the donor gene of interest AND identifi-
able polymorphisms between the two strains of mice. Those mice with
the donor gene of interest, and the highest percentage of
host
markers,
are then used for the next generation of backcrossing. This method
reduces the number of generations of breeding by a factor of 2, thus
reducing the time needed to produce the congenic line from 3 years to
years or less.
D.
Transgenic mice
Introduction
One of the most useful features of using mice in biomedical research
is the ability to manipulate their genomes, either inserting genes or func-
tionally deleting them. This has made it possible not only to investigate
the properties of individual genes in the whole animal context (what
do the genes do? how does it differ in different tissues?), but also to
generate animal models for human diseases.
A transgenic organism is one in which foreign DNA has been inte-
grated into their germ line (sperm or eggs, as opposed to somatic cells)
by experimental introduction. Transgenics can be animals or plants. In
the biomedical sciences, mice have been particularly amenable to trans-
genic technology. They have been used to study the regulation of gene
function, the role of particular genes in cell development, and for the
production of mouse models for human diseases, to name but a few.
The first transgenic mouse was reported in 1980 by Gordon and Ruddle
(43). The ability of the transgene to be transmitted in the germline was
demonstrated the following year by a number of groups of investiga-
tors, including this one. From these first reports, barely 23 years ago,
thousands of transgenic mouse lines have now been produced in many
different laboratories.
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