| First Author | Burberry A | Year | 2016 |
| Journal | Sci Transl Med | Volume | 8 |
| Issue | 347 | Pages | 347ra93 |
| PubMed ID | 27412785 | Mgi Jnum | J:240357 |
| Mgi Id | MGI:5883181 | Doi | 10.1126/scitranslmed.aaf6038 |
| Citation | Burberry A, et al. (2016) Loss-of-function mutations in the C9ORF72 mouse ortholog cause fatal autoimmune disease. Sci Transl Med 8(347):347ra93 |
| abstractText | C9ORF72 mutations are found in a significant fraction of patients suffering from amyotrophic lateral sclerosis and frontotemporal dementia, yet the function of the C9ORF72 gene product remains poorly understood. We show that mice harboring loss-of-function mutations in the ortholog of C9ORF72 develop splenomegaly, neutrophilia, thrombocytopenia, increased expression of inflammatory cytokines, and severe autoimmunity, ultimately leading to a high mortality rate. Transplantation of mutant mouse bone marrow into wild-type recipients was sufficient to recapitulate the phenotypes observed in the mutant animals, including autoimmunity and premature mortality. Reciprocally, transplantation of wild-type mouse bone marrow into mutant mice improved their phenotype. We conclude that C9ORF72 serves an important function within the hematopoietic system to restrict inflammation and the development of autoimmunity. |
