AI Article Synopsis
- Genetic studies over the last 40 years have identified key genes linked to Alzheimer's disease and related dementias, but translating these findings into animal models has been challenging.
- The GR-AD project aims to create mouse lines that closely replicate the genetics of Alzheimer's by replacing mouse genes with their human counterparts.
- Each model will include a control line with a normal human allele and variant lines that carry specific harmful mutations or risk variants, allowing for more accurate disease modeling.
Article Abstract
Introduction: Genetic studies conducted over the past four decades have provided us with a detailed catalog of genes that play critical roles in the etiology of Alzheimer's disease (AD) and related dementias (ADRDs). Despite this progress, as a field we have had only limited success in incorporating this rich complexity of human AD/ADRD genetics findings into our animal models of these diseases. Our primary goal for the gene replacement (GR)-AD project is to develop mouse lines that model the genetics of AD/ADRD as closely as possible.
Methods: To do this, we are generating mouse lines in which the genes of interest are precisely and completely replaced in the mouse genome by their full human orthologs.
Results: Each model set consists of a control line with a wild-type human allele and variant lines that precisely match the human genomic sequence in the control line except for a high-impact pathogenic mutation or risk variant.
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|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC11032548 | PMC |
| http://dx.doi.org/10.1002/alz.13730 | DOI Listing |
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