Biomedical Engineering Reference
In-Depth Information
C.
Congenic strains of mice
Before it became possible to experimentally introduce genes into
mice, the idea of producing congenic strains of mice was developed. A
congenic mouse is one which is genetically identical to an inbred strain
of mice, with the exception of a gene and other closely-linked genes that
have been purposely bred onto the inbred strain. The desired gene can
be selected on the basis of phenotype, such as a coat color character-
istic, a histocompatibility antigen, a gene that predisposes the animal
towards autoimmune disease, or cancer susceptibility, as examples. In
producing a congenic line of mice, however, the gene of interest is not
the only gene that is selected for. All closely linked genes to the selected
gene that are not removed by recombination during the breeding are
also present in the new strain of mice. The amount of genetic material
surrounding the selected gene that remains is therefore random and
impossible to control.
A congenic line of mice is derived initially by mating two strains of
animals, for example, C57BL/10 (a substrain of C57) and DBA/2 (also
a substrain of DBA). If you want to breed a particular marker from the
DBA/2 strain onto C57BL/10 mice, you would select the progeny from
this mating (the F1 progeny) and backcross it to a C57BL/10 mouse. The
offspring of this crossing would then be tested for the DBA/2 marker, and
positive offspring would be bred to a C57BL/10 mouse again. By con-
tinuing this strategy of backcrossing, you would eventually select for a
mouse whose genetic composition was derived from C57BL/10, but with
the marker, and closely related genes, from the DBA/2 mouse. After 10
or more generations of backcrossing (the more, the better!), the back-
crossed offspring with the DBA/2 marker are intercrossed and tested
for homozygosity of the donor DBA/2 marker. This yields (in theory) a
mouse homozygous for all genes from the parental C57BL/10 strain,
except for the selected genes. These mice can then be inbred as the
congenic strain of mice. In this particular example, the congenic strain
of mice that was developed is called “B10.D2”.
One investigator (Edward Golub) likened the production of a congenic
strain of mice to making a very dry martini containing an olive, starting
with a glass of vermouth containing an olive, and a bottle of gin. Mix
the vermouth with an equal part of gin (the F1 generation). Remove half
of the mix, and replace it with gin, always keeping the olive. Take this
first “backcross” generation and repeat, always removing half of the mix,
replacing it with gin, and keeping the olive. Eventually, you will have a
glass with very little vermouth, but still containing the olive. Similarly, in
producing congenic lines, each generation of backcrossing “dilutes out”
the unwanted genes, without throwing out the gene of interest.
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