International Mammalian Genome Society

The 15th International Mouse Genome Conference (2001)


Dr. Lorraine Flaherty
Wadsworth Center
P.O. Box 22002
New Scotland Avenue
Albany, NY 12201-2002

Co-Authors:  Bolivar V, and Cook M
Institution:   Genomics Institute, Wadsworth Center

Mapping of quantitative trait loci  by the use of knockout/congenic strains

We have recently explored the use of knockout/congenic mouse strains for isolating and mapping quantitative trait loci (QTLs). Since most knockout strains are also congenic strains that have retained a short piece of 129 genetic material, flanking the target ablated locus and derived from 129 embryonic stem cells, they can also be used to test for polymorphisms surrounding the target locus.  There are over 50 of these knockout/congenic strains commercially available and represent a unique source for QTL mapping. To investigate the utility of this resource, we have used these strains to identify regions that affect certain behaviors in mice, including open field activity.  We have also developed a testing scheme to enable the separation of flanking and target gene effects on behavioral performance.  In our screens for open field activity, we have found that at least two knockout/congenic strains, B6-IL10-/- and B6-Cd28-/-, behave differently than B6.  In further testing with B6-IL10-/-, we have found that flanking 129 genetic material (surrounding the target locus) is responsible for the different behavior of these mice.  These observations are in accord with the works of others that map a QTL for open field activity to chr 1. This scheme has several distinct advantages to conventional protocols since it yields a ready-made congenic strain as well as allows repeated observations of genetically similar mice.

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