Gene replacement-Alzheimer's disease (GR-AD): Modeling the genetics of human dementias in mice

Kellie Benzow, Kul Karanjeet, Adrian L. Oblak, Gregory W. Carter, Michael Sasner, Michael D. Koob

Research output: Contribution to journalArticlepeer-review

2 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)3080-3087
Number of pages8
JournalAlzheimer's and Dementia
Volume20
Issue number4
DOIs
StatePublished - Apr 2024

Bibliographical note

Publisher Copyright:
© 2024 The Authors. Alzheimer's & Dementia published by Wiley Periodicals LLC on behalf of Alzheimer's Association.

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

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