B6-hATXN3 Mouse

Spinocerebellar ataxias (SCAs) are a group of genetic diseases that mainly manifest as chronic progressive ataxia, such as limping, sudden falls, and difficulty in pronunciation. The main lesion sites of these diseases are the cerebellum and its associated tissues. They are mostly inherited in an autosomal dominant manner, but there are also autosomal recessive and X-linked inheritance types. The average incidence of SCA is 2.7 per 100,000 people ^[1]. SCA can be divided into repeat expansion type and non-repeat expansion type according to the genetic mutation type. Among them, repeat expansion type includes polyglutamine SCA and non-translated region repeat expansion type SCA. Spinocerebellar ataxia type 3 (SCA3), also known as Machado-Joseph disease (MJD), belongs to polyglutamine SCA and is the most common dominant hereditary ataxia. The pathogenesis of SCA3 is the loss of neurotransmitters caused by CAG repeat expansion in the ATXN3 gene. This expansion results in a long polyglutamine (polyQ) domain in the Ataxin 3 protein, leading to protein aggregation and dysfunction of the ubiquitin-proteasome system. The CAG repeat number in the healthy human ATXN3 gene ranges from 12 to 44, while the polyQ domain of SCA3 patients abnormally increases, with CAG repeat numbers ranging from 56 to 87. Individuals with CAG repeat numbers between 45 and 55 exhibit incomplete penetrance of SCA3 symptoms. Like other PolyQ diseases, the CAG repeat number is negatively correlated with the age of onset of SCA3 and positively correlated with the severity of the disease ^[2-3].

Currently, most SCA treatments targeting the ATXN3 gene are in the early stages of development and mainly involve reducing abnormal ATXN3 expression through means such as miRNA or ASO drugs. The Ataxin 3 protein in mice does not contain or only contains a shorter polyQ structure. Considering the differences between humans and mice in terms of genes, humanizing mouse genes can help accelerate these treatments into clinical stages. This strain is a mouse Atxn3 gene humanized model that can be used for research on Spinocerebellar ataxia type 3 (SCA3) ^[4-9]. The homozygous B6-hATXN3 mice are viable and fertile. Additionally, based on the independently developed TurboKnockout fusion BAC recombination technology, Cyagen can also generate hot mutation models based on this strain and provide customized services for specific mutations to meet experimental needs in pharmacology.