Faculty Articles
Publication Title
Hypertension
Publisher
American Heart Association
ISSN
0194-911X
Publication Date
6-1-2017
Keywords
Angiotensin II, Animals, Arterial Pressure, Disease Models, Animal, Drug Resistance, Genes, RAG-1, Genotype, Heart Rate, Hypertension, Kidney Glomerulus, Male, Mice, Mice, Inbred C57BL, Mice, Knockout, Mice, Transgenic, Random Allocation, Recombination, Genetic
Abstract
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 5 independent laboratories including ours before 2015, has been lost. In mice purchased from Jackson Laboratory in 2015 and 2016, the time course and magnitude increase in mean arterial pressure induced by 2 weeks of Ang II infusion at 490 ng/kg per minute was identical between B6.Rag1−/−-M and male wild-type littermates. Moreover, there were no differences in the time course or magnitude increase in mean arterial pressure at the lowest dose of Ang II (200 ng/kg per minute) that increased mean arterial pressure. This loss in Ang II resistance is independent of T cells. Angiotensin type 1-receptor binding was 1.4-fold higher in glomeruli isolated from recently purchased B6.Rag1−/−-M suggesting an increase in renal angiotensin type 1-receptor 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. Finally, these observations illustrate the importance of including experimental details about the location and time period over which animals are bred in publications involving animal studies to promote rigor and reproducibility in the scientific literature.
DOI
10.1161/HYPERTENSIONAHA.117.09063
Volume
69
Issue
6
First Page
1121
Last Page
1127
Disciplines
Medicine and Health Sciences | Pharmacy and Pharmaceutical Sciences
NSUWorks Citation
Ji, Hong; Pai, Amrita V; West, Crystal A; Wu, Xie; Speth, Robert Charles; and Sandberg, Kathryn, "Loss of Resistance to Angiotensin II-Induced Hypertension in the Jackson Laboratory Recombination-Activating Gene Null Mouse on the C57BL/6J Background" (2017). Faculty Articles. 108.
https://nsuworks.nova.edu/hpd_corx_facarticles/108
Comments
This work was supported by grants from the National Institutes of Health: TL1-TR001431 (A.V. Pai), UL1-TR001409 (K. Sandberg) and R01-HL119380 (K. Sandberg and H. Ji).