TG-hATXN3 (85Q) Mouse

The ATXN3 gene encodes Ataxin 3, a protein primarily responsible for intracellular protein degradation and involved in various cellular processes including DNA repair and autophagy. The ATXN3 gene is widely expressed in the human brain and other tissues, with particularly high expression levels in the cerebellum and spinal cord ^[1]. Spinocerebellar Ataxia type 3 (SCA3), also known as Machado-Joseph Disease (MJD), is a progressive neurodegenerative disorder characterized clinically by motor coordination impairment (cerebellar ataxia), bulbar, pyramidal, and extrapyramidal dysfunction, and may be accompanied by peripheral neuropathy or ophthalmoplegia ^[2]. SCA3 is the most common dominantly inherited ataxia, caused by an abnormal expansion of CAG repeat sequences in the ATXN3 gene. This expansion leads to the formation of an elongated polyglutamine (polyQ) domain in the Ataxin 3 protein, subsequently causing protein aggregation and dysfunction of the ubiquitin-proteasome system. Among polyglutamine diseases, the prevalence of SCA3 is second only to Huntington's disease (HD). The number of CAG repeats in the ATXN3 gene of healthy individuals typically ranges from 12 to 44, whereas affected individuals with SCA3 have 56 to 87 repeats. Individuals with 45 to 55 repeats may exhibit incomplete penetrance of SCA3 symptoms. Similar to other polyglutamine diseases, the length of the CAG repeat is negatively correlated with the age of onset and positively correlated with the severity of SCA3 ^[2-3].

This strain represents a SCA3 disease model generated through transgenic technology, expressing a human ATXN3 gene carrying approximately 85 CAG repeats (Q). The number of CAG repeats (Q) in the human ATXN3 gene in this model is associated with the more severe forms of SCA3. Preliminary research data indicate that 2-month-old TG-hATXN3(85Q) mice exhibit a significant increase in stride width and a shortened latency to fall in the rotarod test, suggesting impairments in motor coordination and activity. Therefore, this strain can be utilized for research on the ubiquitin-proteasome system and the pathogenic mechanisms of SCA3, as well as for the screening, development, and evaluation of targeted therapeutic drugs.