Evidence map›Paper›PMID 38491505›Full record

ArticleFluids and barriers of the CNS2024

Abcg2a is the functional homolog of human ABCG2 expressed at the zebrafish blood-brain barrier.

Joanna R Thomas, William J E Frye, Robert W Robey, Andrew C Warner, Donna Butcher, Jennifer L Matta, Tamara C Morgan, Elijah F Edmondson, Paula B Salazar, Suresh V Ambudkar and 1 more

Erratum issuedOpen access · goldAbstract read
In one paragraph

Article in Fluids and barriers of the CNS, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 7 papers.

0numbers the graph read from it
0cells of the map it votes in
7citing papers in PubMed
1.7field-weighted citation impact, top 14% 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

7 citing papers in PubMed, 8 citations in OpenAlex.

  1. Article
  2. Article
  3. Article
  4. Review
  5. Article
  6. Progress in characterizing ABC multidrug transporters in zebrafish.Drug resistance updates : reviews and commentaries in antimicrobial and anticancer chemotherapy · 2024
    Article
  7. Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

11 authors at 2 institutions in 2 countries.

Joanna R ThomasLaboratory of Cell Biology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, 37 Convent Drive, Room 2108, Bethesda, MD, 20892, USA.
William J E FryeLaboratory of Cell Biology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, 37 Convent Drive, Room 2108, Bethesda, MD, 20892, USA.
Robert W RobeyLaboratory of Cell Biology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, 37 Convent Drive, Room 2108, Bethesda, MD, 20892, USA.
Andrew C WarnerMolecular Histopathology Laboratory, Frederick National Laboratory for Cancer Research, Frederick, MD, USA.
Donna ButcherMolecular Histopathology Laboratory, Frederick National Laboratory for Cancer Research, Frederick, MD, USA.
Jennifer L MattaMolecular Histopathology Laboratory, Frederick National Laboratory for Cancer Research, Frederick, MD, USA.
Tamara C MorganMolecular Histopathology Laboratory, Frederick National Laboratory for Cancer Research, Frederick, MD, USA.
Elijah F EdmondsonMolecular Histopathology Laboratory, Frederick National Laboratory for Cancer Research, Frederick, MD, USA.
Paula B SalazarLaboratory of Cell Biology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, 37 Convent Drive, Room 2108, Bethesda, MD, 20892, USA.
Suresh V AmbudkarLaboratory of Cell Biology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, 37 Convent Drive, Room 2108, Bethesda, MD, 20892, USA.
Michael M GottesmanLaboratory of Cell Biology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, 37 Convent Drive, Room 2108, Bethesda, MD, 20892, USA. mgottesman@nih.gov.
National Institutes of Health · USFrederick National Laboratory for Cancer Research · US

Funding

Biochemical Analysis of Multidrug Resistance-linked Transport ProteinsZIABC010030 · NCI · DIVISION OF BASIC SCIENCES - NCI · PI AMBUDKAR, SURESH · 2009 to 2025
$21.6M
Zebrafish model of blood-brain barrier to improve drug delivery to the brainZIABC012052 · NCI · DIVISION OF BASIC SCIENCES - NCI · PI GOTTESMAN, MICHAEL · 2021 to 2025
$3.5M
6 · The paper itself

Abstract

backgroundA principal protective component of the mammalian blood-brain barrier (BBB) is the high expression of the multidrug efflux transporters P-glycoprotein (P-gp, encoded by ABCB1) and ABCG2 (encoded by ABCG2) on the lumenal surface of endothelial cells. The zebrafish P-gp homolog Abcb4 is expressed at the BBB and phenocopies human P-gp. Comparatively little is known about the four zebrafish homologs of the human ABCG2 gene: abcg2a, abcg2b, abcg2c, and abcg2d. Here we report the functional characterization and brain tissue distribution of zebrafish ABCG2 homologs.

methodsTo determine substrates of the transporters, we stably expressed each in HEK-293 cells and performed cytotoxicity and fluorescent efflux assays with known ABCG2 substrates. To assess the expression of transporter homologs, we used a combination of RNAscope in situ hybridization probes and immunohistochemistry to stain paraffin-embedded sections of adult and larval zebrafish.

resultsWe found Abcg2a had the greatest substrate overlap with ABCG2, and Abcg2d appeared to be the least functionally similar. We identified abcg2a as the only homolog expressed at the adult and larval zebrafish BBB, based on its localization to claudin-5 positive brain vasculature.

conclusionsThese results demonstrate the conserved function of zebrafish Abcg2a and suggest that zebrafish may be an appropriate model organism for studying the role of ABCG2 at the BBB.

Indexed as

ATP Binding Cassette Transporter, Subfamily G, Member 2Blood-Brain BarrierZebrafishAdultAnimalsEndothelial CellsHEK293 CellsHumansMammalsNeoplasm ProteinsABCG2 protein, humanATP Binding Cassette Transporter, Subfamily G, Member 2Neoplasm ProteinsABCG2Blood–brain barrierDrug resistanceZebrafish

Identifiers

PMID38491505
PMCPMC10941402
OpenAlexW4392863521

What OpenQuestion holds

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LicenceCC BY
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.