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The Journal of Neuroscience, March 15, 2003, 23(6):2426

Genetic Mapping of Variation in Spatial Learning in the Mouse

Daniela Steinberger^{1, 2, *}, David S. Reynolds^{3, *}, Pushpindar Ferris³, Rachael Lincoln³, Susmita Datta¹, Joanna Stanley³, Andrea Paterson³, Gerard R. Dawson³, and Jonathan Flint¹

¹ Wellcome Trust Centre for Human Genetics, Oxford, OX3 7BN, United Kingdom, ² Bioscientia, Center for Human Genetics, 55218 Ingelheim, Germany, and ³ Merck Sharp and Dohme Research Laboratories, The Neuroscience Research Centre, Terlings Park, Essex, CM20 2QR United Kingdom

Inbred strains of mice are known to differ in their performance in the Morris water maze task, a test of spatial discrimination and place navigation in rodents, but the genetic basis of individual variation in spatial learning is unknown. We have mapped genetic effects that contribute to the difference between two strains, DBA/2 and C57BL6/J, using an F2 intercross and methods to detect quantitative trait loci (QTL). We found two QTL, one on chromosome 4 and one on chromosome 12, that influence behavior in the probe trial of the water maze (genome-wide significance p = 0.017 and 0.015, respectively). By including tests of avoidance conditioning and behavior in a novel environment, we show that the QTL on chromosomes 4 and 12 specifically influence variation in spatial learning. QTL that influence differences in fearful behavior (on chromosomes 1, 3, 7, 15, and 19) operate while mice are trained in the water maze apparatus.

Key words: quantitative trait locus; spatial learning; mouse genetics; water maze; genetic mapping; conditioned fear

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^* D.S. and D.S.R. contributed equally to this work.

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Copyright © 2003 Society for Neuroscience  0270-6474/03/2362426-08$05.00/0

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