Abstract
The CD3 ζ chain (CD247), a gene involved in T-cell signaling, has been shown to associate with blood pressure in human genetic studies. To test the functional role of CD247 in hypertension and renal disease, zinc-finger nucleases targeting CD247 were injected into Dahl salt-sensitive (SS/JrHsdMcwi) embryos. The resulting 11-bp frameshift deletion in exon 1 of CD247 led to a predicted premature stop codon. Western blotting confirmed the absence of CD247 protein in the thymus, and flow cytometry (n=5-9 per group) demonstrated that the mutant rats (CD247) have a >99% reduction in circulating CD3 T cells compared with littermate controls (CD247). Studies were performed on age-matched, littermate male, CD247 and CD247 rats fed a 4.0% NaCl diet for 3 weeks. The infiltration of CD3 T cells into the kidney after high salt was significantly blunted in CD247 (1.4±0.4×10 cells per kidney) when compared with that in the CD247 (8.7±2.0×10 cells per kidney). Accompanying the reduced infiltration of T cells, mean arterial blood pressure was significantly lower in CD247 than in CD247 (134±1 versus 151±2 mm Hg). As an index of kidney disease, urinary albumin and protein excretion rates were significantly reduced in CD247 (17±1 and 62±2 mg/d, respectively) when compared with that in CD247 (49±3 and 121±5 mg/d, respectively). Glomerular and renal tubular damage were also attenuated in the CD247. These studies demonstrate that functional T cells are required for the full development of Dahl salt-sensitive hypertension and indicate that the association between CD247 and hypertension in humans may be related to altered immune cell function.
Original language | English (US) |
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Pages (from-to) | 559-564 |
Number of pages | 6 |
Journal | Hypertension |
Volume | 63 |
Issue number | 3 |
DOIs | |
State | Published - Mar 2014 |
Externally published | Yes |
Keywords
- hypertension
- immune system
- kidney
- lymphocytes
- rats
ASJC Scopus subject areas
- Internal Medicine