Evidence map›Paper›PMID 31201215›Full record

ArticleeNeuro

Targeting Microglia Using Cx3cr1-Cre Lines: Revisiting the Specificity.

Xiao-Feng Zhao, Mahabub Maraj Alam, Yuan Liao, Tingting Huang, Ramkumar Mathur, Xinjun Zhu, Yunfei Huang

Abstract read
In one paragraph

Article in eNeuro. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 69 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
69citing papers in PubMed, 1 pooled it
–field-weighted citation impact
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

69 citing papers in PubMed, 1 synthesis or guideline pooled it.

  1. Pooled it
  2. Article
  3. Article
  4. Article
  5. Article
  6. Article
  7. Article
  8. Review
  9. Article
  10. Article
  11. Article
  12. Article
  13. Article
  14. Article
  15. Article
  16. A common Iba1 antibody labels vasopressin neurons in mice.bioRxiv : the preprint server for biology · 2025
    Article
  17. Article
  18. Article
  19. The Arp2/3 complex is required forbioRxiv : the preprint server for biology · 2025
    Article
  20. Article

9 more citing papers are in PubMed but not listed here.

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

7 authors.

Xiao-Feng ZhaoDepartment of Neuroscience and Experimental Therapeutics, Albany Medical College, Albany, NY 12208.
Mahabub Maraj AlamDepartment of Neuroscience and Experimental Therapeutics, Albany Medical College, Albany, NY 12208.
Yuan LiaoDepartment of Molecular and Cellular Physiology, Albany Medical College, Albany, NY 12208, USA.
Tingting HuangDepartment of Neuroscience and Experimental Therapeutics, Albany Medical College, Albany, NY 12208.
Ramkumar MathurDepartment of Molecular and Cellular Physiology, Albany Medical College, Albany, NY 12208, USA.
Xinjun ZhuDepartment of Molecular and Cellular Physiology; the IBD Center, Division of Gastroenterology, Department of Medicine, Albany Medical College, Albany, NY 12208.
Yunfei HuangDepartment of Neuroscience and Experimental Therapeutics, Albany Medical College, Albany, NY 12208 huangy@amc.edu.ORCID 0000-0002-7129-1250

Funding

Understanding the role of microglia on epileptogenesisR01NS093045 · NINDS · ALBANY MEDICAL COLLEGE · PI HUANG, YUNFEI · 2015 to 2018
$1.4M
The mTOR pathway in neuronal death and epileptogenesisR01NS062068 · NINDS · ALBANY MEDICAL COLLEGE · PI HUANG, YUNFEI · 2008 to 2011
$1.2M
NHE3 Polymorphisms and Chronic Diarrheal DiseasesK08DK088950 · NIDDK · ALBANY MEDICAL COLLEGE · PI ZHU, XINJUN · 2010 to 2014
$691k
Regulation of NHE3 by the mTOR/autophagy pathways in diarrheal diseasesR03DK099566 · NIDDK · ALBANY MEDICAL COLLEGE · PI ZHU, XINJUN · 2013 to 2014
$158k
NIDDK NIH HHS R03 DK099566NINDS NIH HHS R01 NS062068NINDS NIH HHS R01 NS093045
6 · The paper itself

Abstract

Microglia play a pivotal role in maintaining homeostasis of the CNS. There is growing interest in understanding how microglia influence normal brain function and disease progression. Several microglia-specific Cx3cr1-Cre lines have been developed and have become indispensable tools in many investigations of microglial function. However, some recent studies have reported that these lines may have significant leakage into neurons. Other studies have reported that Cx3cr1 is expressed in non-microglial cells, including neurons and astrocytes, in vitro or in vivo either during brain development or upon neurological insult. All these reports raise serious concerns about the trustworthiness of these Cre-lines and whether the conclusions drawn from previous studies are valid. Here, we found that a floxed fluorescent reporter mouse line which has been frequently used to verify Cre lines displayed spontaneous expression of the GFP reporter, independent of Cre recombinase, thus revealing a potential caveat in assessing cre lines. We further confirmed that two Cx3cr1-Cre mouse lines can drive fluorescent reporter expression largely restrictively in microglia. Finally, we clarified that these two mouse lines maintain microglia-specific expression even following excitatory injury. Together, our findings confirm that two previously created Cx3cr1-Cre lines remain as invaluable tools for studying microglia. Moreover, to ensure the quality of data generated and the soundness of conclusions drawn from such data, it should be compulsory to thoroughly examine reporter lines for spontaneous leakiness when labeling cells to study CNS function and diseases.

Indexed as

Gene ExpressionAnimalsAstrocytesBrainCX3C Chemokine Receptor 1FemaleGenes, ReporterGreen Fluorescent ProteinsIntegrasesMaleMice, TransgenicMicrogliaNeuronsReproducibility of ResultsCre recombinaseCX3C Chemokine Receptor 1Cx3cr1 protein, mouseGreen Fluorescent ProteinsIntegrasescrecx3cr1epilepsymicrogliareportertracing

Identifiers

PMID31201215
PMCPMC6620394

What OpenQuestion holds

Textmetadata
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.