Analysis of Rat Chromosome 9 for Genetic Determinants of Blood Pressure
Abstract (Summary)BP QTL on the Rat Chromosome 9(RNO9) have been previously shown to have a significant BP lowering effect when trapped in congenic strains developed by selective backcrossing of the Dahl salt-sensitive (S) and Dahl salt-resistant (R) strain. One such S.R(9) congenic strain, S.R(9)x3x2C had a significantly lower BP than the S rat and this effect was lost in the S.R(9)x3x2Cx1 sub-strain derived from the S.R(9)x3x2C strain. The R alleles trapped in the S.R(9)x3x2Cx1 strain were also a part of the S.R(9)x3x2Bx1 strain which is an adjoining congenic strain also having a significantly lower BP compared to the S rat. These differences were attributed to the genetic elements trapped in the congenic strains. To test this hypothesis and to examine if there were any interactions between the genetic elements or the now fragmented parts of the BP QTL, real-time gene expression of the genes in the overlapping part of the three congenic strains were performed. Significant differences in the expression were found suggesting a complex mechanism for the BP control in this region. Differential atrial ANP content between S and R rats is clearly documented at a young age of 4-6 weeks. Since the relationship between the genetic factors dictating atrial ANP content and the genetic factors controlling BP (BP) is not known, these congenic strains were tested for atrial ANP content at two time points -4 weeks and 1 day neonatal animals. Significant differences were found between the different strains and matched the trend in the BP measured in the strains. This provides evidence to the link between atrial ANP content and BP in two possible ways, as a sensitive marker at a pre-hypertensive age for future hypertension and as a major phenomenon for genetically controlled pathogenesis for hypertension.
School Location:USA - Ohio
Source Type:Master's Thesis
Keywords:rat congenic chromosome genetic hypertension
Date of Publication:01/01/2008