Speed Congenics
 Congenic
mouse strains were first developed during the 1940s
to investigate tissue graft rejection. Derivation
of a congenic strain involves the transfer of a mutation
(or any genetic region of interest) from one genetic
background, often an ill-defined mix of several mouse
strains, onto the defined background of an inbred
strain. Traditionally, this is done by successive
backcrosses of mutant “donors” to inbred
“recipient” mice. According to Mendel’s
Laws, the amount of donor strain genome is reduced
by 50% with each generation (Figure
1).
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After 10 backcross generations – with accompanying
selection for the mutation of interest – a congenic
strain is theoretically 99.9% identical to the recipient
inbred strain except for loci flanking the genetic region
of interest. The time frame for development of a conventional
congenic strain is 2.5-3 years, which is often incompatible
with the pace of modern scientific research.
The “speed congenic” approach takes advantage
of the fact that over 6000 DNA microsatellite markers
have now been mapped on the mouse genome. Many of these
are polymorphic between inbred strains. Microsatellite
polymorphisms are exploited to optimize backcrossing
through selection of progeny that contain the highest
percentage of the recipient strain genome at each generation
( Figure 2).
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Ideally 2-3 female mice carrying the genetic region of interest are
outcrossed to a male of the recipient strain to assure that all males
of the F1 generation will carry the Y chromosome from the recipient
strain at the beginning of the speed congenics project. Two to three
male F1 animals carrying the genetic region of interest are then
backcrossed to recipient-strain females to produce N2 progeny.
Assuming no problems with breeding or health, etc. marker-assisted
backcrossing allows for >99% recipient genome content
to be reached after only five generations (N5), thereby
reducing the time frame to 12-14 months (Figure
3). At N5, siblings can be intercrossed to generate
congenic mice that are homozygous for the mutation or
genetic region of interest. |
LASP Speed Congenics Services
The Laboratory Animal Sciences Program (LASP) at NCI-Frederick
offers “speed congenics” production for NIH/NCI-affiliated
investigators. |
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Production of congenic mice in 12-14 months
(assuming no problems with breeding, health, genotyping,
etc.) |
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Consultation in strain background selection
and genetic screening strategy |
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Analysis of resulting mice for recipient
strain genome contribution |
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Generation of homozygous or heterozygous
congenics |
| Since the scope
of speed congenic projects can vary greatly depending
on the number of mutations to be transferred and the genetic
backgrounds involved, please use the CSAS/Accessions System
for cost estimates on individual
projects. |
Contact Information
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