Document Type
Article
Publication Date
4-1-2024
Original Citation
Benzow K,
Karanjeet K,
Oblak A,
Carter GW,
Sasner M,
Koob M.
Gene replacement-Alzheimer's disease (GR-AD): Modeling the genetics of human dementias in mice. Alzheimers Dement. 2024;20(4):3080-7
Keywords
JMG, Humans, Animals, Mice, Alzheimer Disease, tau Proteins, Mutation, Presenilin-1, Amyloid beta-Protein Precursor
JAX Source
Alzheimers Dement. 2024;20(4):3080-7
ISSN
1552-5279
PMID
38343132
DOI
https://doi.org/10.1002/alz.13730
Grant
National Institute on Aging; National Institutes of Health, Grant/Award Numbers: R61/R33NS115089, R56AG067573, RF1AG079125
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.
Comments
This is an open access article under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.