[A mice model of amyotrophic lateral sclerosis expressing mutant human FUS protein].

Abstract

UNLABELLED:

BACKGROUND AND ОBJECTIVE: Loss of conformation and function of sufficient number of proteins with high aggregation capacity plays an important role in the pathogenesis of many neurodegenerative disorders (NDD). Due to a recent discovery of new array of proteins with the capacity to form aggregates of nonamyloid type, new NDD models as well as a new level of understanding in vivo models which are already exist is needed. DNA/RN A binding proteins - FUS and TDP-43 play a crucial role in the pathogenesis of some forms of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia. The objective of the study was to develop a new ALS transgenic model.

MATERIAL AND METHODS:

In cell culture experiments, we studied mutant FUS proteins capable to form intracellular deposits morphologically similar to those observed in the autopsy material of ALS patients.

RESULTS AND CONCLUSION:

We created a transgenic mice line, in which a pathogenic form of human FUS protein was expressed in the nervous system. That led to the aggregation of FUS protein in spinal cord and motor neurons with the following degeneration and development of a phenotype, similar to the human ALS disease phenotype, in young grown-up animals. This neurodegenerative phenotype corresponds to a great number of clinical manifestations of human ALS and is an adequate transgenic model of the disease.

• Authors: A V Deĭkin, E A Kovrazhkina, R K Ovchinnikov, E V Bronovitskiĭ, O D Razinskaia, A P Smirnov, T G Ermolkevich, A B Eliakov, A N Popov, E N Fedorov, O A Lytkina, M S Kukharskiĭ, T V Tarasova, T A Shelkovnikova, A A Ustiugov, N N Ninkina, I L Gol'dman, E R Sadchikova, S O Bachurin, V I Skvortsova
• Journal: Zhurnal nevrologii i psikhiatrii imeni S.S. Korsakova (Zh Nevrol Psikhiatr Im S S Korsakova) Vol. 114 Issue 8 Pg. 62-9 ( 2014) ISSN: 1997-7298 [Print] Russia (Federation)
• PMID: 25345633 (Publication Type: English Abstract, Journal Article)

Chemical References

• RNA-Binding Protein FUS

Topics

• Amyotrophic Lateral Sclerosis (genetics, metabolism)
• Animals
• Disease Models, Animal
• Humans
• Mice
• Mice, Transgenic
• Mutation
• RNA-Binding Protein FUS (genetics, metabolism)
• Real-Time Polymerase Chain Reaction
• Spinal Cord (metabolism)