Establishment of a humanized SCA2 mouse model carrying a CAA disruption preventing CAG repeat expansion in pathogenic genes.

ABSTRACT:

Background

Spinocerebellar ataxia type 2 (SCA2) is a neurodegenerative disease marked by significant clinical and genetic heterogeneity, primarily caused by expanded CAG mutations in the ATXN2 gene. The unstable expansion of CAG repeats disrupts the genetic stability of animal models, which is detrimental to disease research.

Methods

In this study, we established a mouse model in which CAG repeats do not undergo microsatellite instability (MSI) across generations. A humanized ATXN2 cDNA with four CAA interruptions within 73 CAG expansions was inserted into the Rosa26 locus of C57BL/6J mice. A 23 CAG control mouse model was also generated to verify ATXN2 integration and expression.

Results

In our model, the number of CAG repeats remained stable during transmission, wit

SUBMITTER: Zhang Y 

PROVIDER: S-EPMC12531100 | biostudies-literature | 2025 Sep

REPOSITORIES: biostudies-literature