Generation of an Atxn2-CAG100 knock-in mouse reveals N-acetylaspartate production deficit due to early Nat8l dysregulation

Neurobiology of Disease
Nesli-Ece SenGeorg Auburger

Abstract

Spinocerebellar ataxia type 2 (SCA2) is an autosomal dominant neurodegenerative disorder caused by CAG-expansion mutations in the ATXN2 gene, mainly affecting motor neurons in the spinal cord and Purkinje neurons in the cerebellum. While the large expansions were shown to cause SCA2, the intermediate length expansions lead to increased risk for several atrophic processes including amyotrophic lateral sclerosis and Parkinson variants, e.g. progressive supranuclear palsy. Intense efforts to pioneer a neuroprotective therapy for SCA2 require longitudinal monitoring of patients and identification of crucial molecular pathways. The ataxin-2 (ATXN2) protein is mainly involved in RNA translation control and regulation of nutrient metabolism during stress periods. The preferential mRNA targets of ATXN2 are yet to be determined. In order to understand the molecular disease mechanism throughout different prognostic stages, we generated an Atxn2-CAG100-knock-in (KIN) mouse model of SCA2 with intact murine ATXN2 expression regulation. Its characterization revealed somatic mosaicism of the expansion, with shortened lifespan, a progressive spatio-temporal pattern of pathology with subsequent phenotypes, and anomalies of brain metabolites suc...Continue Reading

Citations

Nov 27, 2019·International Journal of Molecular Sciences·Nesli-Ece SenGeorg Auburger
Jul 24, 2020·International Journal of Molecular Sciences·Jana KeySuzana Gispert
Jun 26, 2020·Frontiers in Neuroscience·Anna Niewiadomska-CimickaYvon Trottier
Sep 17, 2020·International Journal of Molecular Sciences·Aleksandar ArsovićGeorg Auburger
Feb 7, 2021·Movement Disorders : Official Journal of the Movement Disorder Society·Luis E Almaguer-MederosGeorg Auburger
Feb 14, 2021·Journal of Huntington's Disease·Jasmine DonaldsonLesley Jones
Mar 10, 2021·Nutritional Neuroscience·Tania Rodriguez-GrañaLuis Velázquez-Pérez

❮ Previous
Next ❯

Related Concepts

Related Feeds

Amyloid Lateral Sclerosis

Amyotrophic Lateral Sclerosis (ALS) is a progressive nervous system disease associated with the death of neurons that control voluntary muscles. Discover the latest research on ALS here.