The major focus of my lab is to understand molecular cues that control the radia l growth of axons and death of motor neurons. Radial growth of axons is studied in mice by ES cell mediated homologous recombination. Motor neurons disease is s tudied in mouse models of amyotrophic lateral sclerosis (ALS) in transgenic mice for neurofilaments and superoxide dismutase 1 (SOD1). During development, axons undergo two major changes. First, the long, thin axons make growth cones and establish stable synapses. Second, axonal volume increase s 100 fold, and large myelinated axons accumulate large numbers of neurofilament s (NFs). NFs are 10 nm filaments composed of NF-H (200 kd), NF-M (150 kd) and N F-L (68 kd) subunits. Genetic analysis has shown a direct correlation between t he number of filaments and axonal volume. Our transgenic mouse models have indi cated that subunit ratios play a critical role in controlling radial growth of a xons. Recent gene deletion analysis on individual subunits indicate that NF-L i s important for filament formation; NF-M is important for filament assembly and control of filament number. In order to identify the domains of NF subunits tha t are responsible for controlling the radial growth of axons, a systematic domai n deletion approach is being used. We have successfully produced mice for carbox yl terminal deletions of NF-M and NF-H, and analyses of these mice are in progre ss. Approximately 2% of human ALS patients have mutations in the gene encoding for S OD1. A hallmark of ALS is neurofilament accumulation in cell bodies and proxima l axons. Over 50 mutations in SOD1 have been identified in human ALS patients. A large number of mouse models exist for ALS. The role of each NF subunit in d isease onset and progression of motor neuron death is unknown. In order to addr ess this question, NF-H deleted and over-expressing mice are bred with SOD1 over -expressing mice and efforts are underway to characterize these mice. Results will indicate the role of NF-H in motor neuron-mediated cell death.
Rao, Mala V; Campbell, Jabbar; Palaniappan, Arti; Kumar, Asok; Nixon, Ralph A
Journal of neurochemistry.
Correction to: Impact of nonoptimal intakes of saturated, polyunsaturated, and trans fat on global burdens of coronary heart disease. [J Am Heart Assoc. (2016) 5, e002891.] Doi:10.1161/JAHA.115.002891
Wang, Q; Afshin, A; Yakoob, M Y; Singh, G M; Rehm, C D; Khatibzadeh, S; Micha, R; Shi, P; Mozaffarian, D; Ezzati, M; Fahimi, S; Wirojratana, P; Powles, J; Elmadfa, I; Rao, M; Alpert, W; Lim, S S; Engell, R E; Andrews, K G; Abbott, P A; Abdollahi, M; Abeya, Gilardon E O; Ahsan, H; Al, Nsour M A A; Al-Hooti, S N; Arambepola, C; Fernando, D N; Barennes, H; Barquera, S; Baylin, A; Becker, W; Bjerregaard, P; Bourne, L T; Capanzana, M V; Castetbon, K; Chang, H -Y; Chen, Y; Cowan, M J; Riley, L M; De, Henauw S; Ding, E L; Duante, C A; Duran, P; Barbieri, H E; Farzadfar, F; Hadziomeragic, A F; Fisberg, R M; Forsyth, S; Garriguet, D; Gaspoz, J -M; Gauci, D; Calleja, N; Ginnela, B N V; Guessous, I; Gulliford, M C; Hadden, W; Haerpfer, C; Hoffman, D J; Houshiar-Rad, A; Huybrechts, I; Hwalla, N C; Ibrahim, H M; Inoue, M; Jackson, M D; Johansson, L; Keinan-Boker, L; Kim, C -I; Koksal, E; Lee, H -J; Li, Y; Lipoeto, N I; Ma, G; Mangialavori, G L; Matsumura, Y; McGarvey, S T; Fen, C M; Monge-Rojas, R A; Musaiger, A O; Nagalla, B; Naska, A; Ocke, M C; Oltarzewski, M; Szponar, L; Orfanos, P; Ovaskainen, M -L; Tapanainen, H; Pan, W -H; Panagiotakos, D B; Pekcan, G A; Petrova, S; Piaseu, N; Pitsavos, C; Posada, L G; Sanchez-Romero, L M; Selamat, R B T; Sharma, S; Sibai, A M; Sichieri, R; Simmala, C; Steingrimsdottir, L; Swan, G; Sygnowska, E H; Templeton, R; Thanopoulou, A; Thorgeirsdottir, H; Thorsdottir, I; Trichopoulou, A; Tsugane, S; Turrini, A; Vaask, S; van, Oosterhout C; Veerman, J L; Verena, N; Waskiewicz, A; Zaghloul, S; Zajkas, G
Journal of the American Heart Association.