Data in support of: Atrophin-1 antisense oligonucleotide provides robust protection from pathology in a fully humanized DRPLA model

Dentatorubral-pallidoluysian atrophy (DRPLA) is a fatal neurodegenerative disease arising from a CAG repeat expansion in the atrophin-1 (ATN1) gene. Because DRPLA, like many repeat expansion disorders (REDs), arises predominantly from toxic gain-of-function mechanisms, we hypothesized that ATN1 knockdown would have therapeutic potential. To test this, we established the first fully humanized mouse model of a RED, in which one allele of mouse Atn1 is completely replaced by human ATN1, including 112 pure CAG repeats. This novel approach to exploring RED biology provides significant advantages, notably the ability to test sequence-specific therapeutics targeting human sequences, even in introns and untranslated regions of pre-mRNA. We found that our model—the Atn1Q112/+ mouse—recapitulates key features of human DRPLA, including behavioral alterations, reduced brain size, and aggregate accumulation. We treated Atn1Q112/+ mice with antisense oligonucleotides (ASOs) targeting mouse Atn1 (to p..., , # Data in support of: Atrophin-1 antisense oligonucleotide provides robust protection from pathology in a fully humanized DRPLA model

Dataset DOI: [10.5061/dryad.1vhhmgr7k](https://doi.org/10.5061/dryad.1vhhmgr7k)

## Description of the data and file structure

Dataset and R scripts used to generate all statistics and figures for the associated manuscript are deposited here in the .xlsx file 'ATN1_manuscript_rProject_source_data.xlsx'.

The .xlsx file comprises 24 separate worksheets with a leading number (e.g. 02C, 03Ac, etc.) which indicates where the data was used in the manuscript, along with a short identifying text (e.g. Cortex ATN1 Levels) which gives additional context about what the data corresponds to. Each worksheet and it's column headings are defined below.

Corresponding R scripts for analysis are also included. R scripts pull data from the .xlsx sheet and make plots and/or run statistics used in the manuscript and include basic annotation. R script naming follows the sam...,