Abstract 320: Gata5 Null Mice: A New Genetic Model Of Low-Renin Salt-Sensitive Hypertension
Bibliographic record
Abstract
GATA5, a transcription factor of the GATA family, is expressed in the kidney where its function is unknown. In mice, inactivation of GATA5 leads to a cardiac hypertrophy similar to that observed in hypertension. We hypothesized that GATA5 in the kidney may participate in blood pressure (BP) regulation. Blood pressure was measured by tail-cuff in 3-5 month old GATA5 null (G5-KO) mice and their Wild-type (Wt) littermates. Systolic BP was higher in G5-KO mice when compared to Wt in both males (143±4 vs 122±3 mm Hg, p<0.001, n=14-15) and females (137±2 vs 117±3 mm Hg, p<0.001, n=11-12). High salt diet (8% NaCl for 6 weeks) further increased BP in G5-KO mice (p<0.05) but not in Wt. Under regular diet, there were no changes in water consumption (Wt: 4.0±0.2 ml/24h; vs KO-G5: 4.1±0.1 ml/24h) and urine excretion (Wt: 1.3±0.1 ml/24h; vs KO-G5: 1.1±0.1 ml/24h). Aldosterone urinary concentration was unchanged (Wt: 16.8±2.0 pmol/24h; vs KO-G5: 16.9±1.2 pmol/24h) as well as urinary and plasmatic electrolytes (Na+, K+, Cl-) concentrations. We determined that GATA5 was mainly expressed in the proximal tubule. Expression of genes coding proteins involved in sodium reabsorption in that segment (or others) was either unchanged (NHE3, NKCC2 and aENAC) or decreased (αNaK-ATPase -15% p<0.05; βENaC -21% p<0.01) in G5-KO mice. Renin expression was also decreased by 40% (p<0.05). In contrast, renal expression of pro-inflammatory genes was increased in G5-KO mice (MCP1 +155% p<0.005, PAI1 +90% p<0.01, RANTES +95% p<0.01) but the number of macrophages (assessed by F4/80 immunostaining) in kidney was not different and Masson’s trichrome staining revealed no fibrosis. In contrast, periodic acid Schiff staining showed glomerular hypercellularity in KO-G5 mice (p<0.05). Older G5-KO mice (10 months) exhibited more severe lesions: focal segmental glomerulosclerosis with mesangial cell proliferation, glomerular basement membrane thickening and accumulation of mesangial extracellular matrix. In summary, G5-KO mice are characterized by hypertension, salt sensitivity and glomerular lesions. They represent a new genetic model to study low-renin hypertension (which affects up to 25% of the hypertensive population) and for which the underlying mechanisms remain incompletely understood.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.001 | 0.000 |
| Meta-epidemiology (narrow) | 0.002 | 0.001 |
| Meta-epidemiology (broad) | 0.001 | 0.001 |
| Bibliometrics | 0.001 | 0.001 |
| Science and technology studies | 0.001 | 0.001 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.001 | 0.001 |
| Research integrity | 0.002 | 0.003 |
| Insufficient payload (model declined to judge) | 0.010 | 0.004 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".