Optineurin is co-localized with FUS in basophilic inclusions of ALS with FUS mutation and in basophilic inclusion body disease
We recently reported that mutations in the gene encoding optineurin (OPTN) cause amyotrophic lateral sclerosis (ALS) . In that report, we demonstrated the co-localization of OPTN with TAR DNA-binding protein of 43 kDa (TDP-43) or Cu/Zn superoxide dismutase (SOD1) in the pathognomonic inclusions of sporadic (SALS) or familial ALS (FALS) with mutated SOD1, respectively .
Fused in sarcoma (FUS) is another causative gene of ALS [1, 7]. FUS-immunoreactivity is identifiable in basophilic inclusions (BIs) from patients with sporadic basophilic inclusion body disease (BIBD)  and in those from ‘FALS with FUS mutation’ patients. The fact that both FUS and OPTN cause ALS when mutated prompted us to investigate the correlation between these proteins.
We analyzed postmortem material from three patients with sporadic BIBD and from three with FALS with FUS mutation. All the patients manifested upper and lower motor neuron signs, but no cognitive impairment was noted. Their demographic and...
KeywordsAmyotrophic Lateral Sclerosis Lower Motor Neuron Double Immunofluorescence Staining Familial Amyotrophic Lateral Sclerosis Anterior Horn Cell
This work was supported in part by grants-in-aid for scientific research from the Japan Society for the Promotion of Science (No. 21500336) and from the Japan Science and Technology Agency (AS2211173G). We thank Dr. Toshio Oyama (Yamanashi Prefectural Central Hospital) for providing materials from ‘FALS with FUS mutation’ patient No. 1, and Drs. Makoto Arai and Haruhiko Akiyama (Tokyo Institute of Psychiatry) for genetic analysis of ‘FALS with FUS mutation’ patient No. 3.
Conflict of interest
The authors report no conflicts of interest.
- 1.Kwiatkowski TJ Jr, Bosco DA, Leclerc AL, Tamrazian E, Vanderburg CR, Russ C, Davis A, Gilchrist J, Kasarskis EJ, Munsat T, Valdmanis P, Rouleau GA, Hosler BA, Cortelli P, de Jong PJ, Yoshinaga Y, Haines JL, Pericak-Vance MA, Yan J, Ticozzi N, Siddique T, McKenna-Yasek D, Sapp PC, Horvitz HR, Landers JE, Brown RH Jr (2009) Mutations in the FUS/TLS gene on chromosome 16 cause familial amyotrophic lateral sclerosis. Science 323:1205–1208PubMedCrossRefGoogle Scholar
- 2.Maruyama H, Morino H, Ito H, Izumi Y, Kato H, Watanabe Y, Kinoshita Y, Kamada M, Nodera H, Suzuki H, Komure O, Matsuura S, Kobatake K, Morimoto N, Abe K, Suzuki N, Aoki M, Kawata A, Hirai T, Kato T, Ogasawara K, Hirano A, Takumi T, Kusaka H, Hagiwara K, Kaji R, Kawakami H (2010) Mutations of optineurin in amyotrophic lateral sclerosis. Nature 465:223–226PubMedCrossRefGoogle Scholar
- 7.Vance C, Rogelj B, Hortobágyi T, De Vos KJ, Nishimura AL, Sreedharan J, Hu X, Smith B, Ruddy D, Wright P, Ganesalingam J, Williams KL, Tripathi V, Al-Saraj S, Al-Chalabi A, Leigh PN, Blair IP, Nicholson G, de Belleroche J, Gallo JM, Miller CC, Shaw CE (2009) Mutations in FUS, an RNA processing protein, cause familial amyotrophic lateral sclerosis type 6. Science 323:1208–1211PubMedCrossRefGoogle Scholar