RGD Reference Report - CD247 modulates blood pressure by altering T-lymphocyte infiltration in the kidney. - Rat Genome Database

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CD247 modulates blood pressure by altering T-lymphocyte infiltration in the kidney.

Authors: Rudemiller, Nathan  Lund, Hayley  Jacob, Howard J  Geurts, Aron M  Mattson, David L  PhysGen Knockout Program,  
Citation: Rudemiller N, etal., Hypertension. 2014 Mar;63(3):559-64. doi: 10.1161/HYPERTENSIONAHA.113.02191. Epub 2013 Dec 16.
RGD ID: 13442481
Pubmed: PMID:24343121   (View Abstract at PubMed)
PMCID: PMC3945169   (View Article at PubMed Central)
DOI: DOI:10.1161/HYPERTENSIONAHA.113.02191   (Journal Full-text)

The CD3 ¿ 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(5) cells per kidney) when compared with that in the CD247(+/+) (8.7±2.0×10(5) 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.



Phenotype Annotations    Click to see Annotation Detail View

Mammalian Phenotype

Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
Cd247Ratabsent alpha-beta T cells  IMP  RGD 
Cd247em1McwiRatabsent alpha-beta T cells  IMP  RGD 
SS-Cd247em1McwiRatabsent alpha-beta T cells  IMP  RGD 
Cd247Ratdecreased B cell number  IMP  RGD 
Cd247em1McwiRatdecreased B cell number  IMP  RGD 
SS-Cd247em1McwiRatdecreased B cell number  IMP  RGD 
Cd247Ratdecreased mean systemic arterial blood pressure inducedIMPcontrolled sodium content dietcompared to wild-typeRGD 
Cd247Ratdecreased mean systemic arterial blood pressure  IMP compared to wild-typeRGD 
Cd247em1McwiRatdecreased mean systemic arterial blood pressure inducedIMPcontrolled sodium content dietcompared to wild-typeRGD 
Cd247em1McwiRatdecreased mean systemic arterial blood pressure  IMP compared to wild-typeRGD 
SS-Cd247em1McwiRatdecreased mean systemic arterial blood pressure inducedIMPcontrolled sodium content dietcompared to wild-typeRGD 
Cd247Ratdecreased T cell number  IMP  RGD 
Cd247em1McwiRatdecreased T cell number  IMP  RGD 
SS-Cd247em1McwiRatdecreased T cell number  IMP  RGD 
Cd247Ratdecreased T cell proliferation  IMP compared to wild-typeRGD 
Cd247em1McwiRatdecreased T cell proliferation  IMP  RGD 
SS-Cd247em1McwiRatdecreased T cell proliferation  IMP  RGD 
Cd247Ratdecreased urine albumin level inducedIMPcontrolled sodium content diet RGD 
Cd247Ratdecreased urine albumin level  IMP  RGD 
Cd247em1McwiRatdecreased urine albumin level inducedIMPcontrolled sodium content diet RGD 
Cd247em1McwiRatdecreased urine albumin level  IMP  RGD 
SS-Cd247em1McwiRatdecreased urine albumin level inducedIMPcontrolled sodium content diet RGD 
Cd247Ratsalt-sensitive hypertension severityIMPcontrolled sodium content diet RGD 
Cd247em1McwiRatsalt-sensitive hypertension severityIMPcontrolled sodium content diet RGD 
SS-Cd247em1McwiRatsalt-sensitive hypertension severityIMPcontrolled sodium content diet RGD 
Objects Annotated

Genes (Rattus norvegicus)
Cd247  (Cd247 molecule)
Cd247em1Mcwi  (Cd247 molecule; zinc finger nuclease induced mutant 1, Medical College of Wisconsin)

Strains
SS-Cd247em1Mcwi  (NA)


Additional Information