Atxn2-flox Mouse

Atxn2, which encodes the polyglutamine (polyQ) protein ataxin-2, is involved in multiple biological functions. It plays a key role in RNA metabolism, stress granules dynamics, endocytosis, calcium signaling, and the regulation of the circadian rhythm. The CAG repeat sequence in the Atxn2 gene encodes a polyQ tract within the ataxin-2 protein [1].

Overexpansion of the CAG repeat in the Atxn2 gene is mainly linked to spinocerebellar ataxia type 2 (SCA2), and intermediate expansions are associated with amyotrophic lateral sclerosis (ALS) and parkinsonism. In SCA2, it leads to autophagy impairment, RNA-mediated toxicity, heightened oxidative stress, and disruption of calcium homeostasis [1]. In ALS, intermediate CAG (polyQ) expansions in Atxn2 are a risk factor, with ≥31 repeats increasing the risk, especially for ALS with frontotemporal dementia [2]. In frontotemporal dementia, while Atxn2 intermediate CAG expansions may not be a major predisposing factor, they can act as a phenotype modifier, with an increased number of CAG repeats associated with an earlier onset, more parkinsonism, and more psychotic symptoms at disease onset [3].

In conclusion, Atxn2 is a multifunctional gene involved in crucial biological processes and is significantly associated with neurodegenerative diseases such as SCA2, ALS, and frontotemporal dementia. The study of Atxn2, especially through in vivo models like gene knockout (KO) or conditional knockout (CKO) mouse models (although not detailed in the given references but generally important in such research), helps in understanding the molecular mechanisms underlying these diseases, potentially paving the way for new therapeutic strategies.