@article{dc251979445b49f5833e10660880d929,
title = "C9orf72 is required for proper macrophage and microglial function in mice",
abstract = "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.",
author = "O'Rourke, {J. G.} and L. Bogdanik and A. Y{\'a}{\~n}ez and D. Lall and Wolf, {A. J.} and Muhammad, {A. K.M.G.} and R. Ho and S. Carmona and Vit, {J. P.} and J. Zarrow and Kim, {K. J.} and S. Bell and Harms, {M. B.} and Miller, {T. M.} and Dangler, {C. A.} and Underhill, {D. M.} and Goodridge, {H. S.} and Lutz, {C. M.} and Baloh, {R. H.}",
note = "Funding Information: We thank V. Funari for assistance with RNA sequencing, A. Cammack for assisting with patient tissue, and A. Koehne for assisting with pathology evaluation. This work was supported by NIH grants NS069669 (R.H.B), NS087351 (C.M.L), GM085796 (D.M.U.), NS078398 (T.M.M.), and UL1TR000124; the Robert and Louise Schwab family; the Cedars-Sinai ALS Research Fund (R.H.B.); and the Cedars-Sinai Board of Governors Regenerative Medicine Institute. T.M.M. has served on medical advisory boards for Ionis Pharmaceuticals and Biogen Idec. Mouse line F12 is available through the Jackson Repository, no. 27068, C57BL/6J-3110043O21Rik<em5Lutzy> /J. RNA-seq data are located in the Gene Expression Omnibus, accession number GSE77681.",
year = "2016",
month = mar,
day = "18",
doi = "10.1126/science.aaf1064",
language = "English",
volume = "351",
pages = "1324--1329",
journal = "Science",
issn = "0036-8075",
number = "6279",
}