Home › Research › Lewy body dementia
C9orf72 is required for proper macrophage and microglial function in mice
O'Rourke JG, Bogdanik L, Yáñez A, Lall D, Wolf AJ, Muhammad AK, Ho R, Carmona S et al.. Science (New York, N.Y.), 2016-03-01
Topic: Brain proteins, microglia and lab models
Expansions of a hexanucleotide repeat (GGGGCC) in the noncoding region of the C9orf72 gene are the most common genetic cause of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia. Decreased expression of C9orf72 is seen in expansion carriers, suggesting that loss of function may play a role in disease. We found that two independent mouse lines lacking the C9orf72 ortholog (3110043O21Rik) in all tissues developed normally and aged without motor neuron disease. Instead, C9orf72 null mice developed progressive splenomegaly and lymphadenopathy with accumulation of engorged macrophage-like cells. C9orf72 expression was highest in myeloid cells, and the loss of C9orf72 led to lysosomal accumulation and altered immune responses in macrophages and microglia, with age-related neuroinflammation similar to C9orf72 ALS but not sporadic ALS human patient tissue. Thus, C9orf72 is required for the normal function of myeloid cells, and altered microglial function may contribute to neurodegeneration in C9orf72 expansion carriers.
Cite this study APA, Vancouver, BibTeX · download .bib or .ris
APA 7th
O'Rourke, J. G., Bogdanik, L., Yáñez, A., Lall, D., Wolf, A. J., Muhammad, A. K., et al. (2016). C9orf72 is required for proper macrophage and microglial function in mice. Science (New York, N.Y.). https://doi.org/10.1126/science.aaf1064
Vancouver
O'Rourke JG, Bogdanik L, Yáñez A, Lall D, Wolf AJ, Muhammad AK, et al. C9orf72 is required for proper macrophage and microglial function in mice. Science (New York, N.Y.). 2016. doi:10.1126/science.aaf1064. PMID: 26989253.
BibTeX
@article{orourke2016-26989253,
author = {O'Rourke, J. G. and Bogdanik, L. and Yáñez, A. and Lall, D. and Wolf, A. J. and Muhammad, A. K. and Ho, R. and Carmona, S. and others},
title = {{C9orf72 is required for proper macrophage and microglial function in mice}},
journal = {Science (New York, N.Y.)},
year = {2016},
doi = {10.1126/science.aaf1064},
pmid = {26989253},
url = {https://doi.org/10.1126/science.aaf1064}
}
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.
Key findings
- Decreased expression of C9orf72 is seen in expansion carriers, suggesting that loss of function may play a role in disease.
- We found that two independent mouse lines lacking the C9orf72 ortholog (3110043O21Rik) in all tissues developed normally and aged without motor neuron disease.
Why it matters
Two mouse lines lacking C9orf72 developed normally without motor neuron disease but showed enlarged spleen and lymph nodes, lysosomal buildup in macrophages and microglia, and age-related neuroinflammation. This suggests that loss of C9orf72 function in immune cells may contribute to disease, but it is mouse work and not a treatment.
Study details
- Evidence strengthLow
Limitations
This is a mouse-model study, and mice lacking a gene entirely do not necessarily reproduce the effects of the partial reduction and toxic repeat expansion seen in human C9orf72 disease, so the negative finding in mice doesn't rule out a role for reduced C9orf72 function in human disease.
How this study scored 56/100
Published in a top-tier 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 | 10 / 10 | Tier 1 — top-tier general journal (Science (New York, N.Y.)) |
| Journal's citation record | 4 / 4 | Science: journal h-index 1,754 (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 | 2016 — 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 554 times (OpenAlex, 2026-10-10) |
| Citations per year | 4 / 5 | 46.2 citations a year over 12 year(s) since 2016 |
| Impact for its field and year | 6 / 6 | Cited 47.4× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 3 / 6 | Cited by 18 other studies in this library |
| Still being cited | 3 / 4 | Cited 96 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 3 / 4 | Last-listed author Robert H. Baloh: h-index 63 (OpenAlex, whole career) |
| Institution's track record | 2 / 3 | Washington University in St. Louis: institution h-index 1,962 (OpenAlex) |
| Multi-centre collaboration | 1 / 3 | OpenAlex lists 3 institution(s) in 1 country |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 26989253) |
| Free to read | 0 / 2 | Behind a paywall — scores zero |
| Total | 56 / 100 | — |
What each of these 20 components measures, and what this score is not →
Read the original
- DOI: 10.1126/science.aaf1064
- PubMed: 26989253
- Original source →
- Free full text: Repository of Digital Objects for Teaching Research and Culture (University of Valencia) →
Full text: free to read — OpenAlex lists this copy as free to read: the link above (checked 6 Feb 1020).
Studies this one cites
Referenced by this study and also in the alzhub library, so you can read them here. Showing 12 of 13.
Later studies that cite this one
18 studies in the alzhub library list this one in their references. Showing the 8 highest-scoring.
Related studies in Lewy body dementia
Also tagged “mice”
1,150 studies in the library carry the topic tag “mice”; these are this study's neighbours in a fixed, alphabetical-by-hash tour of them, not the closest in content. All 1,150 tagged studies.