B6.Rag1 Knockout Mice Generated at the Jackson Laboratory in 2009 Show a Robust Wild-Type Hypertensive Phenotype in Response to Ang II (Angiotensin II).

Abstract

A key finding supporting a causal role of the immune system in the pathogenesis of hypertension is the observation thatknockout mice on a C57Bl/6J background (B6.Rag1), which lack functional B and T cells, develop a much milder hypertensive response to Ang II (angiotensin II) than control C57Bl/6J mice. Here, we report that we never observed any Ang II resistance of B6.Rag1mice purchased directly from the Jackson Laboratory as early as 2009. B6.Rag1mice displayed nearly identical blood pressure increases monitored via radiotelemetry and hypertensive end-organ damage in response to different doses of Ang II and different levels of salt intake (0.02%, 0.3%, and 3% NaCl diet). Similarly, restoration of T-cell immunity by adoptive cell transfer did not affect the blood pressure response to Ang II in B6.Rag1mice. Full development of the hypertension-resistant phenotype in B6.Rag1mice appears to depend on the action of yet unidentified nongenetic modifiers in addition to the absence of functional T cells.