Atxn1, also known as Ataxin-1, is a dosage-sensitive gene with its expression regulation being crucial. While its exact normal function remains to be fully elucidated, it is known to be associated with several neurodegenerative diseases. Pathological polyQ expansion in ATXN1, such as that causing spinocerebellar ataxia type 1 (SCA1), leads to abnormal protein-protein interactions (PPI) [1].

In SCA1 mouse models, Cas9 editing of ATXN1 has shown potential as a treatment approach. A 20% reduction of ATXN1 in the B05 mouse model improved behavior deficits without increasing inflammatory markers, and this approach was also confirmed in human iPSC-derived neurons from SCA1 patients [2]. Additionally, developing a mouse with an amino acid alteration (K772T) in the nuclear localization sequence of expanded ATXN1 protein demonstrated that proper nuclear localization of mutant ATXN1 contributes to many SCA1-like phenotypes including motor and cognitive deficits, and premature lethality [3].

In conclusion, Atxn1 plays a significant role in neurodegenerative diseases, especially SCA1. Mouse models, including those with gene editing and amino-acid alterations, have provided valuable insights into the disease mechanisms related to Atxn1, which may guide the development of therapeutic strategies for SCA1.