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Generation and analysis of new mouse models to determine novel therapeutic targets for Down syndrome-associated cognitive deficits

Award Number: R01HD109750
ORGANIZATION: NATIONAL INSTITUTE OF CHILD HEALTH AND HUMAN DEVELOPMENT
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 09/13/2022
PERIOD OF PERFORMANCE END DATE: 08/31/2027

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Generation and analysis of new mouse models to determine novel therapeutic targets for Down syndrome-associated cognitive deficits - In the United States, Down syndrome occurs in approximately one in every 691 newborns and presents with a constellation of clinical manifestations. It results from human trisomy 21, the most common chromosomal abnormality associated with intellectual disabilities. Currently, there are no effective treatments for the intellectual disabilities linked to Down syndrome, underscoring the urgent need for innovative strategies to develop therapeutic interventions. The mouse remains the premier model organism for studying Down syndrome due to the presence of highly conserved orthologous regions between human chromosome 21 and three mouse genomic segments located on chromosomes 10, 16, and 17. A prevailing hypothesis in Down syndrome research posits that its phenotypes may be causally linked to dosage increases of genes located on human chromosome 21. In line with this hypothesis, extensive efforts have focused on generating and analyzing mouse models that carry an extra copy of these orthologous regions—typically achieved by duplicating the corresponding segments in the mouse genome. These duplication models are often combined with mice carrying targeted deletions of smaller genomic intervals within the duplicated regions to help identify critical dosage-sensitive loci. Progress in this field has been greatly accelerated by advances in Cre/loxP-mediated chromosome engineering technology. To generate long-range chromosomal duplications and deletions in mice via Cre/loxP-mediated recombination, two independent gene targeting events must be performed in mouse embryonic stem cells, followed by Cre-mediated recombination. To support this process, several genetic cassettes are employed, including those encoding antibiotic resistance. In this supplement project, we aim to re-examine an underexplored area of knowledge related to chromosome engineering technology. The success of our efforts will have significant implications for Down syndrome research and broader applications in genetic modeling and analysis.


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 = $565,641 )
2025	2025	HEALTH RESEARCH, INC.	665 ELM ST	BUFFALO	NY	14203	ERIE	USA	Child Health and Human Development Extramural Research	001	4	9/11/2025	SUPPLEMENT FOR EXPANSION	$116,033
2025	2025	HEALTH RESEARCH, INC.	665 ELM ST	BUFFALO	NY	14203	ERIE	USA	Child Health and Human Development Extramural Research	000	4	8/20/2025	NON-COMPETING CONTINUATION	$449,608
														Subtotal = $565,641

Issue Date FY: 2024 ( Subtotal = $892,259 )
2024	2024	HEALTH RESEARCH, INC.	665 ELM ST	BUFFALO	NY	14203	ERIE	USA	Child Health and Human Development Extramural Research	000	3	8/27/2024	NON-COMPETING CONTINUATION	$450,011
2024	2024	HEALTH RESEARCH, INC.	665 ELM ST	BUFFALO	NY	14203	ERIE	USA	Child Health and Human Development Extramural Research	001	3	8/28/2024	SUPPLEMENT FOR EXPANSION	$442,248
														Subtotal = $892,259

Issue Date FY: 2023 ( Subtotal = $898,642 )
2023	2023	HEALTH RESEARCH, INC.	ELM & CARLTON ST	BUFFALO	NY	14263	ERIE	USA	Child Health and Human Development Extramural Research	000	2	8/16/2023	NON-COMPETING CONTINUATION	$460,655
2023	2023	HEALTH RESEARCH, INC.	ELM & CARLTON ST	BUFFALO	NY	14263	ERIE	USA	Child Health and Human Development Extramural Research	001	2	8/30/2023	SUPPLEMENT FOR EXPANSION	$437,987
														Subtotal = $898,642

Issue Date FY: 2022 ( Subtotal = $475,839 )
2022	2022	HEALTH RESEARCH, INC.	ELM AND CARLTON ST	BUFFALO	NY	14263	ERIE	USA	Child Health and Human Development Extramural Research	001	1	9/15/2022	NEW	$14,535
2022	2022	HEALTH RESEARCH, INC.	ELM AND CARLTON ST	BUFFALO	NY	14263	ERIE	USA	Child Health and Human Development Extramural Research	000	1	9/13/2022	NEW	$461,304
														Subtotal = $475,839

Grand Total All Awards = $2,832,381

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Generation and analysis of new mouse models to determine novel therapeutic targets for Down syndrome-associated cognitive deficits

Award Number: R01HD109750

ORGANIZATION: NATIONAL INSTITUTE OF CHILD HEALTH AND HUMAN DEVELOPMENT

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 09/13/2022

PERIOD OF PERFORMANCE END DATE: 08/31/2027

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