Evidence map›Paper›PMID 25716530›Full record

ArticleGene therapy2015

Therapeutic effect of prenatal alkalization and PTC124 in Na(+)/HCO3(-) cotransporter 1 p.W516* knock-in mice.

Y-W Fang, S-S Yang, T Chau, M Nakamura, O Yamazaki, G Seki, H Yamada, H-M Hsu, C-J Cheng, S-H Lin

Open access · bronzeAbstract read
PubMed Publisher
In one paragraph

Article in Gene therapy, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.

0numbers the graph read from it
0cells of the map it votes in
6citing papers in PubMed
0.9field-weighted citation impact, top 26% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

6 citing papers in PubMed, 10 citations in OpenAlex.

  1. Review
  2. Review
  3. Article
  4. Review
  5. A novel mutant NaThe Journal of physiology · 2016
    Article
  6. Clinical potential of ataluren in the treatment of Duchenne muscular dystrophy.Degenerative neurological and neuromuscular disease · 2016
    Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

10 authors at 4 institutions in 3 countries.

Y-W Fang1] Division of Nephrology, Department of Medicine, Shin Kong Wu Ho-Su Memorial Hospital, Taipei, Taiwan [2] Graduate Institute of Medical Science, National Defense Medical Center, Taipei, Taiwan.
S-S Yang1] Graduate Institute of Medical Science, National Defense Medical Center, Taipei, Taiwan [2] Division of Nephrology, Department of Medicine, Tri-Service General Hospital, Taipei, Taiwan.
T ChauDepartment of Medicine, Providence St Vincent Medical Center, Portland, OR, USA.
M NakamuraDepartment of Internal Medicine, Faculty of Medicine, Tokyo University, Tokyo, Japan.
O YamazakiDepartment of Internal Medicine, Faculty of Medicine, Tokyo University, Tokyo, Japan.
G SekiDepartment of Internal Medicine, Faculty of Medicine, Tokyo University, Tokyo, Japan.
H YamadaDepartment of Internal Medicine, Faculty of Medicine, Tokyo University, Tokyo, Japan.
H-M HsuDivision of Nephrology, Department of Medicine, Shin Kong Wu Ho-Su Memorial Hospital, Taipei, Taiwan.
C-J Cheng1] Graduate Institute of Medical Science, National Defense Medical Center, Taipei, Taiwan [2] Division of Nephrology, Department of Medicine, Tri-Service General Hospital, Taipei, Taiwan.
S-H Lin1] Graduate Institute of Medical Science, National Defense Medical Center, Taipei, Taiwan [2] Division of Nephrology, Department of Medicine, Tri-Service General Hospital, Taipei, Taiwan.
Tokyo Medical University · JPTri-Service General Hospital · TWNational Defense Medical Center · TWProvidence St. Vincent Medical Center · US

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

We created Na(+)/HCO3(-) cotransporter 1 (NBCe1) p.W516* knock-in mice as a model of isolated proximal renal tubular acidosis showing early lethality associated with severe metabolic acidosis to investigate the therapeutic effects of prenatal alkalization or posttranscriptional control 124 (PTC124). NBCe1(W516*/W516*) mice were treated with non-alkalization (control, n=12), prenatal alkalization postcoitus (prenatal group, n=7) and postnatal alkalization from postnatal day 6 (postnatal group, n=12). Mutation-specific therapy, PTC124 (60 mg kg(-1)) or gentamicin (30 mg kg(-1)), was administered intraperitoneally from postnatal day 6. Blood and urine biochemistry, acid-base analysis, survival rate and renal histology were examined. NBCe1 protein, mRNA abundance and activity ex vivo were assessed after PTC124 and gentamicin treatment. Prenatal group mice had similar initial body weight to wild-type mice and achieved significant weight gain thereafter compared with controls. They had higher serum bicarbonate level (15.5 ± 1.4 vs 5.5 ± 0.1 mmol l(-1), P<0.05) on postnatal day 14 and better renal function, histology and survival rates (60.8 ± 23.5 vs 41.1 ± 15.8 days, P<0.05) than the postnatal group. Compared with the control and gentamicin therapies, PTC124 therapy significantly increased NBCe1 protein abundance despite unchanged mRNA transcription. Only PTC124 therapy significantly increased survival rate and partially rescued NBCe1 activity ex vivo. In NBCe1(W516*/W516*) mice, prenatal alkali therapy achieved higher survival rates and ameliorated organ dysfunction. PTC124 therapy for this nonsense mutation was partially effective in increasing NBCe1 expression and activity.

Indexed as

Genetic TherapyAcidosis, Renal TubularAlkaliesAnimalsGentamicinsMiceOxadiazolesRNA, MessengerSodium-Bicarbonate SymportersAlkaliesatalurenGentamicinsOxadiazolesRNA, MessengerSlc4a4 protein, mouseSodium-Bicarbonate Symporters

Identifiers

PMID25716530
OpenAlexW1983200696

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.