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Full human gene replacement mouse models of Alzheimer's Disease

Award Number: R01AG079125
ORGANIZATION: NATIONAL INSTITUTE ON AGING
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 09/01/2022
PERIOD OF PERFORMANCE END DATE: 08/31/2027

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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.


Issue Date FY	Funding FY	Legal Entity Name	Legal Entity Address	Legal Entity City	Legal Entity State	Legal Entity Zip Code	Legal Entity COUNTY	Legal Entity COUNTRY	Assistance Listing	Award Code	Budget Year	Action Date	Action Type	Action Amount

Issue Date FY: 2025 ( Subtotal = $1,321,156 )
2025	2025	REGENTS OF THE UNIVERSITY OF MINNESOTA	2221 UNIVERSITY AVE SE STE 100	MINNEAPOLIS	MN	55414	HENNEPIN	USA	Aging Research	000	2	8/19/2025	EXTENSION WITH OR WITHOUT FUNDS	$1,321,156
														Subtotal = $1,321,156

Grand Total All Awards = $1,321,156

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Full human gene replacement mouse models of Alzheimer's Disease

Award Number: R01AG079125

ORGANIZATION: NATIONAL INSTITUTE ON AGING

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

PERIOD OF PERFORMANCE START DATE: 09/01/2022

PERIOD OF PERFORMANCE END DATE: 08/31/2027

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