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This site is dedicated to scientific community working on ALS. Our aim is to optimize researchers time and efforts by providing updated, well organized information on novel findings, available resources and research support.
AriSLA - The Foundation for research on ALS - has been set up to make ALS research investments more effective and efficient, to speed up the clinical research impact e and to provide patients with better care, improved conditions and life expectancy. Its aim is to boost Italian excellencies in basic, clinical and technological research. The Foundation founders are Fondazione Cariplo, Fondazione Telethon, Fondazione Vialli and Mauro and AISLA.

 

 

C9ORF72 repeat expansions in mice cause TDP-43 pathology, neuronal loss, and behavioral deficits

Abstract

The major genetic cause of frontotemporal dementia and amyotrophic lateral sclerosis is a G4C2 repeat expansion in C9ORF72. Efforts to combat neurodegeneration associated with "c9FTD/ALS" are hindered by a lack of animal models recapitulating disease features. We developed a mouse model to mimic both neuropathological and clinical c9FTD/ALS phenotypes. We expressed (G4C2)66 throughout the murine central nervous system by means of somatic brain transgenesis mediated by adeno-associated virus. Brains of 6-month-old mice contained nuclear RNA foci, inclusions of poly(Gly-Pro), poly(Gly-Ala), and poly(Gly-Arg) dipeptide repeat proteins, as well as TDP-43 pathology. These mouse brains also exhibited cortical neuron and cerebellar Purkinje cell loss, astrogliosis, and decreased weight. (G4C2)66-mice also developed behavioral abnormalities similar to clinical symptoms of c9FTD/ALS patients, including hyperactivity, anxiety, antisocial behavior, and motor deficits.

 

Link to download the full article:

http://www.sciencemag.org/content/early/2015/05/18/science.aaa9344.long




     
     
     
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