Behavioural analysis of congenic mouse strains confirms stress-responsive Loci on chromosomes 1 and 12

Abstract

The way in which animals respond to stressful environments correlates with anxiety-related behaviour. To begin identifying the genetic factors that influence anxiety, we have studied the stress-responsiveness of inbred mouse strains using a modified form of the open field activity test (OFA), termed the elevated (e) OFA. In particular, two strains show high (DBA/2J) or low (C57BL/6J) stress-responsiveness in the eOFA. Genetic studies of an F(2) intercross between these two strains previously identified two regions, on chromosomes (Chr) 1 and 12, linked to anxiety-related behaviour. To confirm that these regions contain loci for stress-responsiveness, we established separate congenic mouse strains for the linked Chr1 and Chr12 regions. Each congenic strain harbours a DBA/2J-derived interval encompassing the linked region on the C57BL/6J genetic background: the congenic intervals are between, but not including approximately 48.6 Mb and approximately 194.8 Mb on Chr1, and approximately 36.2 Mb and the distal end of Chr12. Cohorts of DBA/2J, C57BL/6J and congenic mice were analysed for a series of stress-responsive phenotypes using the eOFA test. Both congenic strains had significantly different stress-responsive phenotypes compared to the low-stress C57BL/6J parental strain, but the DBA/2J-derived Chr12 interval had a greater genetic effect than the DBA/2J-derived Chr1 interval for changing the behavioral phenotype of the parental C57BL/6J mouse strain. These results confirmed the presence of stress-responsive loci on Chr1 and Chr12. New stress-related phenotypes were also identified, which aided in comparing and differentiating DBA/2J, C57BL/6J and congenic mice.