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Speed Congenics

Recipient genome content in a conventional backcrossCongenic 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).

Full-Genome Scan of an N4 Backcross Animal 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).
Marker-assisted backcross strategy
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.
Bullet point Production of congenic mice in 12-14 months (assuming no problems with breeding, health, genotyping, etc.)
Bullet point Consultation in strain background selection and genetic screening strategy
Bullet point Analysis of resulting mice for recipient strain genome contribution
Bullet point 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
Wang Ting Hsieh Principal Scientist Phone: 301-846-7132
Email: hsiehwt@mail.nih.gov

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