Human C9ORF72 Hexanucleotide Expansion Reproduces RNA Foci and Dipeptide Repeat Proteins but Not Neurodegeneration in BAC Transgenic Mice

The authors gratefully acknowledge the ALS Association, which funded the generation of these C9BAC mice as well as the ALS/FTD ALS genetics consortium (Lucie Bruijn, Bob Brown, Jonathan Haines, Chris Shaw, Teepu Siddique, and Peggy Vance), which provided the C9ORF72 BAC used in this study. We are grateful to Pin-Tsun Lee for assistance with behavioral testing; the UMass Medical School Electron Microscopy Core Facility, and Kevin Kenna, Elisa Donnard, and the UMASS bioinformatics core for helpful discussions; and Zuoshang Xu and Chunxing Yang for generously supplying antibodies to TDP-43 protein. R.H.B. and C.M. are consultants for Voyager, which did not fund or otherwise participate in this study. They are inventors on a patent filed for the use of rAAV mediated silencing of C9ORF72. L.P. and T.G. have licensed for distribution an antibody to the poly(GP) dipeptide. This work was supported by the National Institutes of Health/National Institute of Neurological Disorders and Stroke R01NS088689 (R.H.B., L.P., C.M., O.M.P.), R21NS089979 (T.F.G.), R01 NS057553 (F.-B.G.), R21NS084528 (L.P.), R01NS063964 (L.P.); R01NS077402 (L.P.); P01NS084974 (L.P.), R01FD004127 (R.H.B.), R01NS079836 (R.H.B.), R01NS065847 (R.H.B.), R01NS073873 (R.H.B.), National Institute of Environmental Health Services R01ES20395 (L.P.), Department of Defense ALSRP AL130125 (L.P.), Mayo Clinic Foundation (L.P.), Mayo Clinic Center for Individualized Medicine (L.P.), ALS Association (R.B., L.P., T.F.G.), Robert Packard Center for ALS Research at Johns Hopkins (L.P., F.-B.G.), Target ALS (L.P., J.K., S.P.B.), ALS Therapy Alliance (F.-B.G., R.H.B.), Grant OD018259 (C.M.), the Angel Fund (R.H.B.), Project ALS (R.H.B.), and the Max Rosenfeld Fund (R.H.B., O.M.P.). H.T. is a Milton Safenowitz Postdoctoral Fellow funded by the ALS Association. O.M.P. is supported by the Michael J. Fox Foundation. J.K. is supported by a National Research Foundation of Korea Fellowship (NRF-2011-357-E00005). S.P.B. is supported by a Klingenstein-Simons Fellowship in the Neurosciences. P.C.S. is supported through the auspices of H.R.H., an Investigator at the Howard Hughes Medical Institute.