Mapping blood pressure loci in (A/J x B6)F2 mice.

Although the genetics of rare, monogenic, forms of human hypertension are fairly well defined, the genetics of the common polygenic form of human essential hypertension is only emerging. With the ability to control environmental variables, animal models have provided valuable tools with which to study blood pressure (BP) homeostasis. We have now studied BP genetics in a model consisting of 1,521 F2 mice from a series of (A/J x B6) intercrosses kept under standardized conditions. Using whole genome quantitative trait loci (QTL) mapping, we have identified four novel significant BP loci. These included Abbp1 on mouse chromosome MMU1 [maximum LOD score (MLS) at approximately 35 cM = 6.8], Abbp2 on MMU4 (MLS at approximately 25 cM = 9.8), Abbp3 on MMU7 (MLS at approximately 25 cM = 5.4), and Abbp4 on MMU11 (MLS at approximately 58 cM = 6.3). Compared with A/J homozygotes, homozygosity for the B6 alleles of Abbp1, Abbp2, or Abbp4 is independently associated with a 7-12 mmHg increase in BP. In contrast Abbp3 interacts epistatically with a locus on MMU17 (near D17Mit180) to modulate BPs in female (A/J x B6)F2 mice. Interestingly, Abbp4 on MMU11 is homologous to a major confirmed BP locus, BP1, on rat chromosome 10 and to a major confirmed BP locus, HYT1, on human chromosome 17. Defining the molecular differences between the A/J and the B6 alleles at these novel loci with major influences on the BP phenotype will contribute to our understanding of the complex genetics of BP control.