RF1AG079125
Project Grant
Overview
Grant Description
Full Human Gene Replacement Mouse Models of Alzheimer's Disease
This application is proposing to continue and expand the collaboration between the Koob Lab at the University of Minnesota and the Model-AD Center. We have developed gene replacement (GR) approaches that allow us to replace mouse genes with their full human orthologue alleles.
The GR targets for this project include many of the human genes most central to the etiology of AD, including APP, PSEN1, PSEN2, and MAPT, as well as genes that play pivotal roles in modulating AD risk, including the APOE gene cluster, the TREM2 gene cluster, the critical region of the MS4A gene cluster, and INPP5D.
A set of models will be generated for each GR target genomic region, consisting of a control line with a WT human genomic sequence, and at least one matching line with either a pathogenic mutation or risk variant in that same human genomic sequence.
Basic QC evaluations of each GR allele will be performed at the University of Minnesota, and Model-AD will then validate them by confirming that each variant line exhibits the expected AD-related endophenotypes.
The human alleles that pass the QC and endophenotype validations will then be incorporated into base AD models with additional AD alleles, with the ultimate goal of recreating the human genetics and pathophysiology of AD as closely as is possible in a mouse.
JAX will distribute all mouse lines generated by this project without restrictions.
This application is proposing to continue and expand the collaboration between the Koob Lab at the University of Minnesota and the Model-AD Center. We have developed gene replacement (GR) approaches that allow us to replace mouse genes with their full human orthologue alleles.
The GR targets for this project include many of the human genes most central to the etiology of AD, including APP, PSEN1, PSEN2, and MAPT, as well as genes that play pivotal roles in modulating AD risk, including the APOE gene cluster, the TREM2 gene cluster, the critical region of the MS4A gene cluster, and INPP5D.
A set of models will be generated for each GR target genomic region, consisting of a control line with a WT human genomic sequence, and at least one matching line with either a pathogenic mutation or risk variant in that same human genomic sequence.
Basic QC evaluations of each GR allele will be performed at the University of Minnesota, and Model-AD will then validate them by confirming that each variant line exhibits the expected AD-related endophenotypes.
The human alleles that pass the QC and endophenotype validations will then be incorporated into base AD models with additional AD alleles, with the ultimate goal of recreating the human genetics and pathophysiology of AD as closely as is possible in a mouse.
JAX will distribute all mouse lines generated by this project without restrictions.
Grant Program (CFDA)
Awarding / Funding Agency
Place of Performance
Minneapolis,
Minnesota
55455
United States
Geographic Scope
Single Zip Code
Regents Of The University Of Minnesota was awarded
Full Human Gene Replacement Mouse Models of Alzheimer's Disease
Project Grant RF1AG079125
worth $4,147,326
from National Institute on Aging in September 2022 with work to be completed primarily in Minneapolis Minnesota United States.
The grant
has a duration of 3 years and
was awarded through assistance program 93.866 Aging Research.
The Project Grant was awarded through grant opportunity Research on Current Topics in Alzheimer's Disease and Its Related Dementias (R01 Clinical Trial Optional).
Status
(Complete)
Last Modified 8/19/22
Period of Performance
9/1/22
Start Date
8/31/25
End Date
Funding Split
$4.1M
Federal Obligation
$0.0
Non-Federal Obligation
$4.1M
Total Obligated
Activity Timeline
Subgrant Awards
Disclosed subgrants for RF1AG079125
Additional Detail
Award ID FAIN
RF1AG079125
SAI Number
RF1AG079125-424471805
Award ID URI
SAI UNAVAILABLE
Awardee Classifications
Public/State Controlled Institution Of Higher Education
Awarding Office
75NN00 NIH NATIONAL INSITUTE ON AGING
Funding Office
75NN00 NIH NATIONAL INSITUTE ON AGING
Awardee UEI
KABJZBBJ4B54
Awardee CAGE
0DH95
Performance District
05
Senators
Amy Klobuchar
Tina Smith
Tina Smith
Representative
Ilhan Omar
Budget Funding
| Federal Account | Budget Subfunction | Object Class | Total | Percentage |
|---|---|---|---|---|
| National Institute on Aging, National Institutes of Health, Health and Human Services (075-0843) | Health research and training | Grants, subsidies, and contributions (41.0) | $4,147,326 | 100% |
Modified: 8/19/22