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Articles by T Ramesh
Total Records ( 1 ) for T Ramesh
  T Ramesh , A. N Lyon , R. H Pineda , C Wang , P. M. L Janssen , B. D Canan , A. H. M Burghes and C. E. Beattie
  Tennore Ramesh, Alison N. Lyon, Ricardo H. Pineda, Chunping Wang, Paul M. L. Janssen, Benjamin D. Canan, Arthur H. M. Burghes, and Christine E. Beattie

Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disorder that, for ~80% of patients, is fatal within five years of diagnosis. To better understand ALS, animal models have been essential; however, only rodent models of ALS exhibit the major hallmarks of the disease. Here, we report the generation of transgenic zebrafish overexpressing mutant Sod1. The construct used to generate these lines contained the zebrafish sod1 gene and ~16 kb of flanking sequences. We generated lines expressing the G93R mutation, as well as lines expressing wild-type Sod1. Focusing on two G93R lines, we found that they displayed the major phenotypes of ALS. Changes at the neuromuscular junction were observed at larval and adult stages. In adulthood the G93R mutants exhibited decreased endurance in a swim tunnel test. An analysis of muscle revealed normal muscle force, however, at the end stage the fish exhibited motoneuron loss, muscle atrophy, paralysis and premature death. These phenotypes were more severe in lines expressing higher levels of mutant Sod1 and were absent in lines overexpressing wild-type Sod1. Thus, we have generated a vertebrate model of ALS to complement existing mammal models.

 
 
 
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