Our two previous linkage studies performed on two F2 (Dahl S×R)-intercross rat populations, one cohort phenotyped for blood pressure 
and another population characterized for navigational performance 
, delineated the potential existence of two closely linked QTLs on chromosome 2, one affecting blood pressure (BP-f4
and the other affecting navigational performance (Nav-8
(). To confirm the existence of these two QTLs in this region, we transferred two Dahl R chromosomal segments spanning the BP-f4/Nav-8
QTLs onto the Dahl S genetic background (). We successfully implemented a “speed congenic” strategy towards the development of highly inbred S.R2A and S.R2B () congenic lines. We performed back-crosses up to back-cross 6 and established homozygous congenic lines for blood pressure measurements and assessment of navigational performance in the Morris water maze (MWM) task. For back-cross 6, the S.R2A congenic line was greater than 99.70% of the Dahl S genetic background and the S.R2B congenic line was greater than 99.77% of the Dahl S genetic background.
Overlapping blood pressure and spatial navigation QTLs detected in F2 (Dahl S×R) intercross rats.
Congenic analysis of BP-f4/Nav-8 QTL region on chromosome 2.
Blood pressure analysis of the congenic lines harboring the chromosome 2 region spanning putative BP-f4
QTLs () substantiated the existence of BP-f4
QTL in this region as demonstrated by the significantly lower systolic, diastolic, and mean blood pressures exhibited by SR.2A congenic rats compared with Dahl S controls (). Introgression of the S.R2A congenic segment onto the Dahl S genetic background lowered systolic blood pressure by 26.0 mmHg (P
0.003, ), diastolic blood pressure by 21.2 mmHg (P
0.01, ), and mean arterial pressure by 23.9 mmHg (P
0.004, ) in females. Blood pressure in S.R2B congenic female rats did not differ from Dahl S female controls, demonstrating the absence of genes affecting blood pressure in this chromosomal region, thus delimiting the chromosomal region to less than 3.3 Mbp (176.6–179.9 Mbp, containing 36 annotated genes, ) that harbors the gene underlying BP-f4
. Similarly, S.R2A congenic males showed significantly lower systolic blood pressure (−30.9 mmHg, P
, ), diastolic blood pressure (−25.7 mmHg, P
, ), and mean arterial pressure (−28.0 mmHg, P
, ) when compared with male controls. Interestingly, we detected significant differences in pulse pressure between S.R2A and Dahl S control rats (P
<0.05, ), suggesting that the gene underlying BP-f4
QTL affects arterial stiffness as well.
Effects of female and male rat chromosome 2 congenic strains on blood pressure.
Annotated genes in rat chromosome 2 176.6–179.9 Mbp region.
Since we detected the Nav-8
QTL in an F2 (Dahl S×R)-intercross male population 
, we evaluated the effect of transferring S.R2A and S.R2B congenic segments onto the Dahl S genetic background on spatial learning and memory by testing S.R2A, S.R2B, and Dahl S control male rats in the Morris water maze (MWM) task to evaluate visiospatial cognition 
Measurements of spatial learning in the MWM task revealed equivalent acquisition performance among all three groups (2,336
>0.2). In the probe trial for spatial memory, all three groups exhibited target selectivity, showing enhanced preference for the target quadrant over other quadrants (, Dahl S male rats: P
<0.001; .R2A male rats: P
<0.001; .R2B male rats: P
<0.001). However, direct comparison of selectivity for the target quadrant in the probe trial showed better performance of Dahl S male controls compared with S.R2A male subjects (<0.001) and equivalent performance when compared with S.R2B male subjects (>0.3). Consistently, Dahl S male rats showed increased spatial accuracy performance when compared with S.R2A male subjects (<0.05), confirming their better search accuracy for the hidden platform.
Testing of spatial learning and memory in Dhal S, S.R2A and S.R2B congenic male rats.
To investigate whether the decreased performance of S.R2A male subjects reflects a male-specific effect on spatial learning and memory or the effect of the congenic segment is independent of sex, we tested S.R2A female subjects and Dahl S female control rats in the MWM task. As shown in , we observed no differences in acquisition (1,216
>0.16) or in the probe trial performance between S.R2A female rats and Dahl S female controls. Both female groups demonstrated target selectivity (, Dahl S female rats: P<0.01; .R2A female rats: P<0.01) and equivalent performance in the probe trial, showing equivalent occupancy of target quadrant () and spatial accuracy performance ().
Testing of spatial learning and memory in Dhal S and S.R2A congenic female rats.