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Dahl (S × R) rat congenic strain analysis confirms and defines a chromosome 17 spatial navigation quantitative trait locus to <10 Mbp.

Herrera VL, Pasion KA, Tan GA, Ruiz-Opazo N - PLoS ONE (2013)

Bottom Line: We developed two congenic strains, S.R17A and S.R17B introgressing Dahl R-chromosome 17 segments into Dahl S chromosome 17 region spanning putative Nav-5 QTL.Performance analysis of S.R17A, S.R17B and Dahl S rats in the Morris water maze (MWM) task showed a significantly decreased spatial navigation performance in S.R17B congenic rats when compared with Dahl S controls (P = 0.02).The S.R17A congenic segment did not affect MWM performance delimiting Nav-5 to the chromosome 17 65.02-74.66 Mbp region.

View Article: PubMed Central - PubMed

Affiliation: Section of Cardiovascular Medicine, Department of Medicine, Boston University School of Medicine, Boston, Massachusetts, United States of America.

ABSTRACT
A quantitative trait locus (QTL) linked with ability to find a platform in the Morris Water Maze (MWM) was located on chromosome 17 (Nav-5 QTL) using intercross between Dahl S and Dahl R rats. We developed two congenic strains, S.R17A and S.R17B introgressing Dahl R-chromosome 17 segments into Dahl S chromosome 17 region spanning putative Nav-5 QTL. Performance analysis of S.R17A, S.R17B and Dahl S rats in the Morris water maze (MWM) task showed a significantly decreased spatial navigation performance in S.R17B congenic rats when compared with Dahl S controls (P = 0.02). The S.R17A congenic segment did not affect MWM performance delimiting Nav-5 to the chromosome 17 65.02-74.66 Mbp region. Additional fine mapping is necessary to identify the specific gene variant accounting for Nav-5 effect on spatial learning and memory in Dahl rats.

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Testing of spatial learning and memory in Dhal S, S.R17A and S.R17B congenic male rats(A) Acquisition performance measured as mean distance in cm during the 24 trials (•, Dahl S; ◊, S.R17A; ○, S.R17B). Percentage distance traveled in quadrants (B, C, D, E) and spatial accuracy performance (F) during the probe trial after completion of Morris water maze training. Quadrants are: target (T), opposite (O), adjacent right (AR) and adjacent left (AL). *P = 0.02, ***P<0.001. Data represent means ± s.e.m. (one-way ANOVA followed by Holm-Sidak’s test for quadrant occupancy in the probe trial of the Morris water maze task and for spatial accuracy performance).
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pone-0058280-g002: Testing of spatial learning and memory in Dhal S, S.R17A and S.R17B congenic male rats(A) Acquisition performance measured as mean distance in cm during the 24 trials (•, Dahl S; ◊, S.R17A; ○, S.R17B). Percentage distance traveled in quadrants (B, C, D, E) and spatial accuracy performance (F) during the probe trial after completion of Morris water maze training. Quadrants are: target (T), opposite (O), adjacent right (AR) and adjacent left (AL). *P = 0.02, ***P<0.001. Data represent means ± s.e.m. (one-way ANOVA followed by Holm-Sidak’s test for quadrant occupancy in the probe trial of the Morris water maze task and for spatial accuracy performance).

Mentions: Measurements of spatial learning in the MWM task revealed equivalent acquisition performance among all three groups (Figure 2A, F2,360 = 1.39, P>0.24). In the probe trial for spatial memory all three groups exhibited target selectivity showing enhanced preference for the target quadrant over other quadrants (Figure 2B, Dahl S rats: P<0.001; Figure 2C, S.R17A rats: P<0.001; Figure 2D, S.R17B rats: P<0.001). However, direct comparison of selectivity for the target quadrant in the probe trial shows better performance of Dahl S controls compared with S.R17B subjects (Figure 2E, P = 0.02) and equivalent performance when compared with S.R17A subjects (Figure 2E, P = 0.79). Consistently, Dahl S rats showed increased spatial accuracy performance when compared with S.R17B subjects (Figure 2F, P = 0.02), corroborating their superior search accuracy for the hidden platform. Navigational performance in S.R17A congenic rats did not differ from Dahl S controls (Figure 2F, P = 0.96) demonstrating absence of genes affecting spatial learning and memory in this chromosomal segment, thus delimiting the chromosomal region to <10 Mbp (65.02–74.66 Mbp) that contains the gene underlying Nav-5.


Dahl (S × R) rat congenic strain analysis confirms and defines a chromosome 17 spatial navigation quantitative trait locus to <10 Mbp.

Herrera VL, Pasion KA, Tan GA, Ruiz-Opazo N - PLoS ONE (2013)

Testing of spatial learning and memory in Dhal S, S.R17A and S.R17B congenic male rats(A) Acquisition performance measured as mean distance in cm during the 24 trials (•, Dahl S; ◊, S.R17A; ○, S.R17B). Percentage distance traveled in quadrants (B, C, D, E) and spatial accuracy performance (F) during the probe trial after completion of Morris water maze training. Quadrants are: target (T), opposite (O), adjacent right (AR) and adjacent left (AL). *P = 0.02, ***P<0.001. Data represent means ± s.e.m. (one-way ANOVA followed by Holm-Sidak’s test for quadrant occupancy in the probe trial of the Morris water maze task and for spatial accuracy performance).
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Related In: Results  -  Collection

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getmorefigures.php?uid=PMC3585172&req=5

pone-0058280-g002: Testing of spatial learning and memory in Dhal S, S.R17A and S.R17B congenic male rats(A) Acquisition performance measured as mean distance in cm during the 24 trials (•, Dahl S; ◊, S.R17A; ○, S.R17B). Percentage distance traveled in quadrants (B, C, D, E) and spatial accuracy performance (F) during the probe trial after completion of Morris water maze training. Quadrants are: target (T), opposite (O), adjacent right (AR) and adjacent left (AL). *P = 0.02, ***P<0.001. Data represent means ± s.e.m. (one-way ANOVA followed by Holm-Sidak’s test for quadrant occupancy in the probe trial of the Morris water maze task and for spatial accuracy performance).
Mentions: Measurements of spatial learning in the MWM task revealed equivalent acquisition performance among all three groups (Figure 2A, F2,360 = 1.39, P>0.24). In the probe trial for spatial memory all three groups exhibited target selectivity showing enhanced preference for the target quadrant over other quadrants (Figure 2B, Dahl S rats: P<0.001; Figure 2C, S.R17A rats: P<0.001; Figure 2D, S.R17B rats: P<0.001). However, direct comparison of selectivity for the target quadrant in the probe trial shows better performance of Dahl S controls compared with S.R17B subjects (Figure 2E, P = 0.02) and equivalent performance when compared with S.R17A subjects (Figure 2E, P = 0.79). Consistently, Dahl S rats showed increased spatial accuracy performance when compared with S.R17B subjects (Figure 2F, P = 0.02), corroborating their superior search accuracy for the hidden platform. Navigational performance in S.R17A congenic rats did not differ from Dahl S controls (Figure 2F, P = 0.96) demonstrating absence of genes affecting spatial learning and memory in this chromosomal segment, thus delimiting the chromosomal region to <10 Mbp (65.02–74.66 Mbp) that contains the gene underlying Nav-5.

Bottom Line: We developed two congenic strains, S.R17A and S.R17B introgressing Dahl R-chromosome 17 segments into Dahl S chromosome 17 region spanning putative Nav-5 QTL.Performance analysis of S.R17A, S.R17B and Dahl S rats in the Morris water maze (MWM) task showed a significantly decreased spatial navigation performance in S.R17B congenic rats when compared with Dahl S controls (P = 0.02).The S.R17A congenic segment did not affect MWM performance delimiting Nav-5 to the chromosome 17 65.02-74.66 Mbp region.

View Article: PubMed Central - PubMed

Affiliation: Section of Cardiovascular Medicine, Department of Medicine, Boston University School of Medicine, Boston, Massachusetts, United States of America.

ABSTRACT
A quantitative trait locus (QTL) linked with ability to find a platform in the Morris Water Maze (MWM) was located on chromosome 17 (Nav-5 QTL) using intercross between Dahl S and Dahl R rats. We developed two congenic strains, S.R17A and S.R17B introgressing Dahl R-chromosome 17 segments into Dahl S chromosome 17 region spanning putative Nav-5 QTL. Performance analysis of S.R17A, S.R17B and Dahl S rats in the Morris water maze (MWM) task showed a significantly decreased spatial navigation performance in S.R17B congenic rats when compared with Dahl S controls (P = 0.02). The S.R17A congenic segment did not affect MWM performance delimiting Nav-5 to the chromosome 17 65.02-74.66 Mbp region. Additional fine mapping is necessary to identify the specific gene variant accounting for Nav-5 effect on spatial learning and memory in Dahl rats.

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