Collectrin, an X-Linked, ACE2 Homologue Causes Hypertension in a Rat Strain through Gene-Gene and Gene-Environment Interactions: Relevance to Human Hypertension
Dr. Cechova and a multi-national investigative team describe a novel model of hypertension in a susceptible murine model.1 Their initial studies of collectrin knockout in a mixed genetic mouse strain did not reveal a significant effect on blood pressure (BP).2 However, prior research demonstrated that the collectrin gene is located on a region of the X chromosome with loci linked to hypertension in humans and rats.3,4 Moreover, renal expression of collectrin is upregulated after subtotal nephrectomy and in salt-sensitive hypertension.
With this background, the authors studied the effects of collectrin null mutations on BP in a 129S6 mouse strain that is susceptible to hypertension and salt sensitivity.5,6 Under standard feeding conditions, the gene-gene interaction in the collectrin knockout/129S6 strain male mice led to a modest 9 mm Hg elevation in BP compared to WT control 129S6 mice. The rise in BP was accompanied by increased left ventricular mass. The investigative team then studied the effects of a high salt diet on BP in these two mice strains. With this gene-environment interaction, BP rose a net 7 mm Hg (15 vs 8 mm Hg) more in collectrin knockout/129S6 male mice than 129S6 male controls over a two week period. The collectrin knockout/129S6 mice manifest evidence for increased superoxide and oxidative stress with decreased nitric oxide. Tempol, a scavenger of radical including superoxide, lowered BP minimally in both mice strains on usual diets and in control 129S6 mice on high salt diets. Tempol lowered BP significantly in the collectrin knockout/129S6 mice on a high salt diet and eliminated the difference in salt sensitive BP responses between the two strains.
- Received September 16, 2013.
- Accepted September 16, 2013.