Abstract

The purpose of the Molecular Genetics core is to (1) assay for mutations in SOD1 and other protein antioxidant genes in genomic DNA samples from all patients analyzed in Project 1; (2) prepare constructs suitable for the synthesis of various forms of tetanus C fragment: SOD1 protein for Project 3; and (3) prepare cDNA constructs with all of the known SOD1 mutations to be available potentially for the other projects as needed. This core unit will be operated within the Day Neuromuscular Research Laboratory under the direction of Dr. Robert Brown. Using standard techniques she routinely now employs in the Day Lab, Dr. Betsy Hosler will perform single strand conformational polymorphism analysis, direct sequencing of PCR products amplified from patients' genomic DNA, preparation and cloning of different tetanus C fragment - SOD1 preparations, PCR amplification of patient SOD1 cDNA from lymphoblastoid cell lines and site directed mutagenesis of wild type SOD1. The services provided by this core will be essential both for patient diagnosis and preparation of experimental reagents for three of the four projects.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute on Aging (NIA)
Type
Research Program Projects (P01)
Project #
1P01AG012992-04
Application #
6267656
Study Section
Project Start
1998-04-15
Project End
1999-03-31
Budget Start
1997-10-01
Budget End
1998-09-30
Support Year
4
Fiscal Year
1998
Total Cost
Indirect Cost

  Institution

Name
Massachusetts General Hospital
Department
Type
DUNS #
City
Boston
State
MA
Country
United States
Zip Code
02199

  Publications

Zhang, Ke; Donnelly, Christopher J; Haeusler, Aaron R et al. (2015) The C9orf72 repeat expansion disrupts nucleocytoplasmic transport. Nature 525:56-61
Matthews, Christopher C; Fishman, Paul S; Wittenberg, George F (2014) Tetanus toxin reduces local and descending regulation of the H-reflex. Muscle Nerve 49:495-501
van Zundert, Brigitte; Peuscher, Marieke H; Hynynen, Meri et al. (2008) Neonatal neuronal circuitry shows hyperexcitable disturbance in a mouse model of the adult-onset neurodegenerative disease amyotrophic lateral sclerosis. J Neurosci 28:10864-74
Ranganathan, Srikanth; Williams, Eric; Ganchev, Philip et al. (2005) Proteomic profiling of cerebrospinal fluid identifies biomarkers for amyotrophic lateral sclerosis. J Neurochem 95:1461-71
Ryu, Hoon; Smith, Karen; Camelo, Sandra I et al. (2005) Sodium phenylbutyrate prolongs survival and regulates expression of anti-apoptotic genes in transgenic amyotrophic lateral sclerosis mice. J Neurochem 93:1087-98
Maxwell, Michele M; Pasinelli, Piera; Kazantsev, Aleksey G et al. (2004) RNA interference-mediated silencing of mutant superoxide dismutase rescues cyclosporin A-induced death in cultured neuroblastoma cells. Proc Natl Acad Sci U S A 101:3178-83
Ulug, Aziz M; Grunewald, Thomas; Lin, Michael T et al. (2004) Diffusion tensor imaging in the diagnosis of primary lateral sclerosis. J Magn Reson Imaging 19:34-9
Klivenyi, Peter; Kiaei, Mahmoud; Gardian, Gabrielle et al. (2004) Additive neuroprotective effects of creatine and cyclooxygenase 2 inhibitors in a transgenic mouse model of amyotrophic lateral sclerosis. J Neurochem 88:576-82
Pasinelli, Piera; Belford, Mary Elizabeth; Lennon, Niall et al. (2004) Amyotrophic lateral sclerosis-associated SOD1 mutant proteins bind and aggregate with Bcl-2 in spinal cord mitochondria. Neuron 43:19-30
Klivenyi, Peter; Calingasan, Noel Y; Starkov, Anatoly et al. (2004) Neuroprotective mechanisms of creatine occur in the absence of mitochondrial creatine kinase. Neurobiol Dis 15:610-7

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