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Exaggerated inflammation, impaired host defense, and neuropathology in progranulin-deficient mice
Yin F, Banerjee R, Thomas B, Zhou P, Qian L, Jia T, Ma X, Ma Y et al.. The Journal of experimental medicine, 2009-12-21
Topic: Brain proteins, microglia and lab models
Progranulin (PGRN) is a widely expressed protein involved in diverse biological processes. Haploinsufficiency of PGRN in the human causes tau-negative, ubiquitin-positive frontotemporal dementia (FTD). However, the mechanisms are unknown. To explore the role of PGRN in vivo, we generated PGRN-deficient mice. Macrophages from these mice released less interleukin-10 and more inflammatory cytokines than wild type (WT) when exposed to bacterial lipopolysaccharide. PGRN-deficient mice failed to clear Listeria monocytogenes infection as quickly as WT and allowed bacteria to proliferate in the brain, with correspondingly greater inflammation than in WT. PGRN-deficient macrophages and microglia were cytotoxic to hippocampal cells in vitro, and PGRN-deficient hippocampal slices were hypersusceptible to deprivation of oxygen and glucose. With age, brains of PGRN-deficient mice displayed greater activation of microglia and astrocytes than WT, and their hippocampal and thalamic neurons accumulated cytosolic phosphorylated transactivation response element DNA binding protein-43. Thus, PGRN is a key regulator of inflammation and plays critical roles in both host defense and neuronal integrity. FTD associated with PGRN insufficiency may result from many years of reduced neutrotrophic support together with cumulative damage in association with dysregulated inflammation.
Key findings
- FTD associated with PGRN insufficiency may result from many years of reduced neutrotrophic support together with cumulative damage in association with dysregulated inflammation.
Why it matters
Mice lacking progranulin showed exaggerated inflammation, impaired host defense and, with age, more microglial and astrocytic activation plus accumulation of phosphorylated TDP-43 in neurons. This suggests frontotemporal dementia from progranulin insufficiency may involve reduced neurotrophic support and dysregulated inflammation, but it is an animal study and reports no treatment or cure.
Study details
- Evidence strengthLow
How this study scored 52/100
Published in a peer-reviewed journal. Scored zero for study design, sample size, effect reported and randomised / blinded because the record does not state it.
| Component | Points | Why |
|---|---|---|
| Journal tier | 7 / 10 | Tier 3 — peer-reviewed journal (The Journal of experimental medicine) |
| Journal's citation record | 4 / 4 | The Journal of Experimental Medicine: journal h-index 652 (OpenAlex, 2026-10-29) |
| Study design | 0 / 12 | No study design recorded — scores zero, not guessed (not stated in the record — scored 0) |
| Strength of evidence | 1 / 5 | Rated “low” in our summary |
| Peer-review validation | 10 / 10 | Peer-reviewed. Published as an article in a named peer-reviewed journal. |
| How recent | 1 / 5 | 2010 — within 20 year(s) of the newest study here |
| Sample size | 0 / 4 | Participant count not stated — scores zero (not stated in the record — scored 0) |
| Effect reported | 0 / 3 | No effect size reported — scores zero (not stated in the record — scored 0) |
| Studied in people | 0 / 3 | Laboratory or animal study (title names “mice”) — scores zero |
| Randomised / blinded | 0 / 2 | No randomisation or blinding stated — scores zero (not stated in the record — scored 0) |
| Times cited | 6 / 7 | Cited 484 times (OpenAlex, 2026-10-10) |
| Citations per year | 4 / 5 | 26.9 citations a year over 18 year(s) since 2010 |
| Impact for its field and year | 4 / 6 | Cited 13.9× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 3 / 6 | Cited by 22 other studies in this library |
| Still being cited | 3 / 4 | Cited 74 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 2 / 4 | Last-listed author Aihao H. Ding: h-index 47 (OpenAlex, whole career) |
| Institution's track record | 2 / 3 | Cornell University: institution h-index 1,649 (OpenAlex) |
| Multi-centre collaboration | 1 / 3 | OpenAlex lists 3 institution(s) in 2 countries |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 20026663) |
| Free to read | 2 / 2 | Free to read |
| Total | 52 / 100 | — |
What each of these 20 components measures, and what this score is not →
Read the original
- DOI: 10.1084/jem.20091568
- PubMed: 20026663
- Original source →
- Free full text: The Journal of Experimental Medicine →
Full text: free to read — OpenAlex lists this copy as free to read: the link above (checked 6 Feb 1020).
Cite this study APA, Vancouver, BibTeX · download .bib or .ris
Built from the record alzhub holds for this paper, not looked up. Volume, issue and page numbers are not held in the record. The record's author list ends in “et al.”, so not every author is named. Check the citation against the original before you use it.
APA 7th
Yin, F., Banerjee, R., Thomas, B., Zhou, P., Qian, L., Jia, T., et al. (2010). Exaggerated inflammation, impaired host defense, and neuropathology in progranulin-deficient mice. The Journal of experimental medicine. https://doi.org/10.1084/jem.20091568
Vancouver
Yin F, Banerjee R, Thomas B, Zhou P, Qian L, Jia T, et al. Exaggerated inflammation, impaired host defense, and neuropathology in progranulin-deficient mice. The Journal of experimental medicine. 2010. doi:10.1084/jem.20091568. PMID: 20026663.
BibTeX
@article{yin2010-20026663,
author = {Yin, F. and Banerjee, R. and Thomas, B. and Zhou, P. and Qian, L. and Jia, T. and Ma, X. and Ma, Y. and others},
title = {{Exaggerated inflammation, impaired host defense, and neuropathology in progranulin-deficient mice}},
journal = {The Journal of experimental medicine},
year = {2010},
doi = {10.1084/jem.20091568},
pmid = {20026663},
url = {https://doi.org/10.1084/jem.20091568}
}
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