Loss of resistance to angiotensin II-induced hypertension in the Jackson Laboratory recombination activating gene null mouse on the C57BL/6J background

摘要

Resistance to angiotensin II (Ang II)-induced hypertension in T-cell deficient male mice with a targeted mutation in the recombination activating gene-1 (Rag1) on the C57BL/6J background (B6.Rag1^−/−-M), which was reported by five independent laboratories including ours prior to 2015, has been lost. In mice purchased from Jackson Laboratory in 2015 and 2016, the time course and magnitude increase in mean arterial pressure (MAP) induced by two weeks of Ang II infusion at 490 ng/kg/min was identical between B6.Rag1^−/−-M and wildtype littermates (B6.WT-M). Moreover, there were no differences in the time course or magnitude increase in MAP at the lowest dose of Ang II (200 ng/kg/min) that increased MAP. This loss in Ang II resistance is independent of T-cells. Angiotensin-type1-receptor (AT1R) binding was 1.4-fold higher in glomeruli isolated from recently purchased B6.Rag1^−/−-M suggesting an increase in renal AT1R activity masks the blood pressure protection afforded by the lack of T-cells. The phenotypic change in B6.Rag1^−/−-M has implications for investigators using this strain to study mechanisms of T-cell modulation of Ang II-dependent blood pressure control. These findings also serve as a reminder that the universal drive for genetic variation occurs in all animals including inbred mouse strains and that spontaneous mutations leading to phenotypic change can compromise experimental reproducibility over time and place. Lastly, these observations illustrate the importance of including experimental details regarding the location and time period over which animals are bred in publications involving animal studies to promote rigor and reproducibility in the scientific literature.