The DOI matches its Crossref record; 20 of the 20 references it cites were found in a registry or an index.
Analysis of Fractalkine Receptor CX3CR1 Function by Targeted Deletion and Green Fluorescent Protein Reporter Gene Insertion
Open accessAbstract
The seven-transmembrane receptor CX(3)CR1 is a specific receptor for the novel CX(3)C chemokine fractalkine (FKN) (neurotactin). In vitro data suggest that membrane anchoring of FKN, and the existence of a shed, soluble FKN isoform allow for both adhesive and chemoattractive properties. Expression on activated endothelium and neurons defines FKN as a potential target for therapeutic intervention in inflammatory conditions, particularly central nervous system diseases. To investigate the physiological function of CX(3)CR1-FKN interactions, we generated a mouse strain in which the CX(3)CR1 gene was replaced by a green fluorescent protein (GFP) reporter gene. In addition to the creation of a mutant CX(3)CR1 locus, this approach enabled us to assign murine CX(3)CR1 expression to monocytes, subsets of NK and dendritic cells, and the brain microglia. Analysis of CX(3)CR1-deficient mice indicates that CX(3)CR1 is the only murine FKN receptor. Yet, defying anticipated FKN functions, absence of CX(3)CR1 interferes neither with monocyte extravasation in a peritonitis model nor with DC migration and differentiation in response to microbial antigens or contact sensitizers. Furthermore, a prominent response of CX(3)CR1-deficient microglia to peripheral nerve injury indicates unimpaired neuronal-glial cross talk in the absence of CX(3)CR1.
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“Cx3cr1-CreERT2 developed by Jung et al. (2000) was reported to drive microglia-specific expression.”
From Targeting Microglia Using Cx3cr1-Cre Lines: Revisiting the Specificity (2019) · cites this paper as Jung et al. (2000)
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“The inducible Cx3cr1-CreERT2 line developed by Jung et al. (2000), displayed some basal cre activity without tamoxifen treatment, but this expression was restricted to microglia.”
From Targeting Microglia Using Cx3cr1-Cre Lines: Revisiting the Specificity (2019) · cites this paper as Jung et al. (2000)
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“The inducible Cx3cr1-CreERT2 line developed by Jung et al. (2000), displayed some basal cre activity without tamoxifen treatment, but this expression was restricted to microglia.”
From Targeting Microglia Using Cx3cr1-Cre Lines: Revisiting the Specificity (2019) · cites this paper as Jung et al. (2000)
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“According to the description on The Jackson Laboratory website, the constitutive Cx3cr1-Cre line created by Jung et al. (2000), displays leakiness into neurons when crossed with a yellow fluorescent protein (YFP) reporter line.”
From Targeting Microglia Using Cx3cr1-Cre Lines: Revisiting the Specificity (2019) · cites this paper as Jung et al. (2000)
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“Thus, the cre activity in this line is not fully dependent on tamoxifen.”
From Targeting Microglia Using Cx3cr1-Cre Lines: Revisiting the Specificity (2019) · cites this paper as Jung et al. (2000)
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“The partial tamoxifen-independent cre activity observed in the Cx3cr1-CreERT2 line developed by Jung et al. (2000), indicates potential embryonic deletion of TSC1 in a fraction”
From Targeting Microglia Using Cx3cr1-Cre Lines: Revisiting the Specificity (2019) · cites this paper as Jung et al. (2000)
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“Microglia were labeled using the CX3CR1+/GFP mouse line in which all microglia express EGFP under the control of fractalkine receptor, CX3CR1, expression (Figure 1, S1, and S5) (Cardona et al., 2006; Jung et al., 2000; Saederup et al., 2010).”
From Microglia Sculpt Postnatal Neural Circuits in an Activity and Complement-Dependent Manner (2012) · cites this paper as Jung et al., 2000
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“CX3CR1 is exclusively expressed by microglia within the brain”
From CX3CR1 Deficiency Alters Microglial Activation and Reduces Beta-Amyloid Deposition in Two Alzheimer's Disease Mouse Models (2010) · cites this paper as [15]
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In the citing paper
“If the YFP reporter line has no spontaneous leakiness, then the constitutive Cx3cr1-Cre line developed by Jung et al. (2000), and which is now available at The Jackson Laboratory, is not microglia specific.”
From Targeting Microglia Using Cx3cr1-Cre Lines: Revisiting the Specificity (2019) · cites this paper as Jung et al. (2000)
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
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“The YFP reporter line was used to verify two inducible Cx3cr1-CreERT2 lines (Jung et al., 2000; Parkhurst et al., 2013).”
From Targeting Microglia Using Cx3cr1-Cre Lines: Revisiting the Specificity (2019) · cites this paper as Jung et al., 2000
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“Nevertheless, tamoxifen treatment led to broad expression of GFP reporter in microglia, without significant leakage into neurons.”
From Targeting Microglia Using Cx3cr1-Cre Lines: Revisiting the Specificity (2019) · cites this paper as Jung et al. (2000)
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“In Cx3Cr1‐eGFP mice, GFP is expressed by CNS‐resident macrophages (Jung et al. 2000), which, as noted above, are predominantly represented by microglia (Zhao et al. 2023).”
From Depletion of Microglia Increases Cortical Oligodendrocyte Density During Remyelination (2026) · cites this paper as Jung et al. 2000
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“the P2ry12 signal co-localized on CX3CR1GFP microglia in which GFP is expressed in resident microglia17,23 (Fig. 4e).”
From Identification of a unique TGF-β–dependent molecular and functional signature in microglia (2014) · cites this paper as [23]
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“Escape behavior is considered to be an active defensive response dependent on increased PVN-CRH+ neuron activity20.”
From Constitutive expression of CX3CR1-BAC-Cre introduces minimal off-target effects in microglia (2026) · cites this paper as [20]
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“The looming-shadow threat task assesses a mouse’s response to a predator-like threat20.”
From Constitutive expression of CX3CR1-BAC-Cre introduces minimal off-target effects in microglia (2026) · cites this paper as [20]
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“No leakiness was reported in those studies.”
From Targeting Microglia Using Cx3cr1-Cre Lines: Revisiting the Specificity (2019) · cites this paper as Jung et al., 2000
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In the citing paper
“which may explain the differences in seizure susceptibility observed in these two studies (Jung et al., 2000; Zhang et al., 2018; Zhao et al., 2018).”
From Targeting Microglia Using Cx3cr1-Cre Lines: Revisiting the Specificity (2019) · cites this paper as Jung et al., 2000
Experimental — accuracy not yet measuredIn the citing paper
“Notably, myeloid priming occurs in cells which express the TFs PU.1 and/or C/EBPα32.”
From Single-cell analysis of mixed-lineage states leading to a binary cell fate choice (2016) · cites this paper as [32]
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Citations
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“Microglia were labeled using the CX3CR1+/GFP mouse line in which all microglia express EGFP under the control of fractalkine receptor, CX3CR1, expression (Figure 1 and see Figures S1 and S5 available online; Cardona et al., 2006; Jung et al., 2000; Saederup et al., 2010).”
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Self-citation
Metadata
- Authors
- Jung, S., Aliberti, J., Graemmel, P., Sunshine, M. J., Kreutzberg, G. W., Sher, A., & Littman, D. R.
- Affiliations
- Howard Hughes Medical Institute (US)
- Immunobiology Section, Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland
- Max Planck Institute of Neurobiology (DE)
- National Institutes of Health (US)
- Corresponding author
- Jung, Steffen
- Venue
- Molecular and Cellular Biology
- Publisher
- Informa UK Limited
- Published
- 2000-06-01
- Volume
- 20
- Issue
- 11
- Pages
- 4106-4114
- ISSN
- 0270-7306 (ISSN-L)
- 1098-5549
- PMC
- PMC85780
- OpenAlex
- W2161057248
- Cited by
- 2,632
- References
- 20
- Citations by year
- 2026: 87 · 2025: 132 · 2024: 172 · 2023: 138 · 2022: 135 · 2021: 192 · 2020: 174 · 2019: 162 · 2018: 136 · 2017: 147 · 2016: 142 · 2015: 140 · 2014: 163 · 2013: 128 · 2012: 95
- FWCI
- 11.19
- Type
- journal article
- Language
- en
- Open access
- green
- europepmc.org
- Locations
- Molecular and Cellular Biology (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Howard Hughes Medical Institute
- Topics
- Health Sciences › Medicine › Oncology › Chemokine receptors and signaling
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Health Sciences › Medicine › Immunology and Allergy › Cell Adhesion Molecules Research
- Keywords
- CX3CR1, fractalkine, CX3C chemokines, G protein-coupled receptors, monocytes, dendritic cells, natural killer cells, microglia, monocyte extravasation, peritonitis, dendritic cell migration, peripheral nerve injury, neuroinflammation
- MeSH terms
- CX3C Chemokine Receptor 1, Animals, Luminescent Proteins, Mice, Mutant Strains, Phenotype, Receptors, HIV, Gene Expression, Mutagenesis, Insertional, Genes, Reporter, Receptors, Cytokine, Gene Targeting, Green Fluorescent Proteins, Mice
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