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.
Keywords: APOE‐GR; APP‐GR; C9ORF72‐GR; MAPT‐GR; PSEN1‐GR; PSEN2‐GR; SNCA‐GR; TARDBP‐GR; TMEM106B‐GR; TREM2‐GR; functional sequence variant; gene‐replacement mouse model; protective haplotype; risk haplotype.
© 2024 The Authors. Alzheimer's & Dementia published by Wiley Periodicals LLC on behalf of Alzheimer's Association.