Submitted on February 7, 2008
Accepted on December 8, 2008
Blood pressure and heart rate QTL in mice of the B6/D2 lineage: sex differences and environmental influences
David A. Blizard1*, Arimantas Lionikas2, David J. Vandenbergh3, Terrie Vasilopoulos4, Glenn S Gerhard5, James W Griffith6, Laura C Klein7, Joseph T Stout2, Holly A Mack2, Joan M Lakoski8, Lars Larsson9, Jeanne M Spicer2, George P Vogler2, and Gerald E McClearn2
1 Ctr. for Development & Heath Genetics, Pennsylvania State University, University Park, Pennsylvania, United States
2 Center for Developmental and Health Genetics, Penn State University, University Park, Pennsylvania, United States
3 Biobehavioral Health, Pennsylvania State University, University Park, Pennsylvania, United States
4 Biobehavioral Health, Penn State, University Park, Pennsylvania, United States; Ctr. for Development & Heath Genetics, Pennsylvania State University, University Park, Pennsylvania, United States
5 Weis Center for Research, Geisinger Medical Center, Danville, Pennsylvania, United States
6 Comparative Medicine, Penn State College of Medicine, Hershey, Pennsylvania, United States
7 Biobehavioral Health, Penn State, University Park, Pennsylvania, United States
8 Department of Pharmacology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, United States
9 Department of Clinical Neurophysiology, Uppsala University, Uppsala, Sweden
* To whom correspondence should be addressed. E-mail: dab22{at}psu.edu.
A quantitative trait locus (QTL) approach was used to define the genetic architecture underlying variation in systolic blood pressure (SBP) and heart rate (HR), measured indirectly on 7 occasions using the tail cuff procedure. The tests were conducted in 395 F2 adult mice (197 males, 198 females) derived from a cross of the C57BL/6J (B6) and DBA/2J (D2) strains and in 22 BXD recombinant-inbred (RI) strains. Interval mapping of F2 data for the first 5 days of measurement nominated one statistically significant and one suggestive QTL for SBP on chromosomes (Chr) 4 and 14, respectively, and two statistically significant QTL for HR on Chr 1 (which was specific to female mice) and Chr 5. New suggestive QTL emerged for SBP on Chr 3 (female-specific) and 8 and for HR on Chr 11 for measurements recorded several weeks after mice had undergone stressful blood sampling procedures. The two statistically significant HR QTL were confirmed by analyses of BXD RI strain means. Male and female F2 mice did not differ in SBP or HR but RI strain analyses showed pronounced strain by sex interactions and a negative genetic correlation between the two measures in both sexes. Evidence for a role for mitochondrial DNA was found for both HR and SBP. QTL for HR and SBP may differ in males and females and may be sensitive to different environmental contexts.
