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Establishment and Characterization of Novel Mutant Mouse Models for the Addiction Research Community

Award Number: U01DA051235
ORGANIZATION: NATIONAL INSTITUTE ON DRUG ABUSE
OPDIV: NIH
AWARD CLASS: COOPERATIVE AGREEMENT
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 08/15/2021
PERIOD OF PERFORMANCE END DATE: 05/31/2026

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Establishment and Characterization of Novel Mutant Mouse Models for the Addiction Research Community - PROJECT SUMMARY/ABSTRACT Addiction is an enormous economic, personal, and social burden, costing over $600 billion per year in the U.S. Understanding vulnerability to addiction, and developing effective therapies, requires identifying the genes and pathways that mediate the addiction process. Our long-term goal is to develop novel genetic models for addiction-relevant phenotypes, and use these models to characterize the genetic mechanisms of addiction. We propose to leverage the Jackson Laboratory Knockout Mouse Project 2 (JAX KOMP2) pipeline to prioritize addiction gene candidates, and then characterize the effects of candidate gene knockouts on addiction-related behaviors and on addiction-relevant tissues. The JAX KOMP2 Phenotyping Center performs high-throughput phenotyping of knockout mice across organ systems using an efficient, broad-based testing pipeline including behavioral assays for emotionality and sleep, both predictive of addiction phenotypes. Here we propose to exploit this rich KOMP2 dataset to select a subset of lines with emotionality and neuronal phenotypes (e.g. deviant open field, light dark, hole board, tail suspension, prepulse inhibition, rotarod, electroconvulsive seizure threshold, or sleep phenotypes) and lacking metabolism and physiology phenotypes. Our preliminary data provide compelling evidence that gene deletions leading to emotionality phenotypes in the KOMP pipeline have addiction phenotypes. We will subject these lines to deep drug abuse–relevant phenotyping, including drug self-administration, transcriptional profiling from key neuronal tissues, and whole brain imaging. The data from these will be integrated using systems analysis. The successful completion of this project will yield dozens of novel mouse models with detailed transcriptome, and neuroanatomical profile to establish mechanistic insight into this behavioral abnormality. These can serve are a resource for the research community for therapeutics development.


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 = $877,994 )
2025	2025	JACKSON LABORATORY	600 MAIN ST	BAR HARBOR	ME	04609	HANCOCK	USA	Drug Use and Addiction Research Programs	001	5	8/14/2025	NON-COMPETING CONTINUATION	$877,994
2025	2024	JACKSON LABORATORY	600 MAIN ST	BAR HARBOR	ME	04609	HANCOCK	USA	Drug Use and Addiction Research Programs	000	4	3/17/2025	NON-COMPETING CONTINUATION	$0
														Subtotal = $877,994

Issue Date FY: 2024 ( Subtotal = $867,363 )
2024	2024	JACKSON LABORATORY	600 MAIN ST	BAR HARBOR	ME	04609	HANCOCK	USA	Drug Use and Addiction Research Programs	000	4	7/17/2024	NON-COMPETING CONTINUATION	$867,363
														Subtotal = $867,363

Issue Date FY: 2023 ( Subtotal = $824,056 )
2023	2023	JACKSON LABORATORY	600 MAIN ST	BAR HARBOR	ME	04609	HANCOCK	USA	Drug Use and Addiction Research Programs	000	3	6/2/2023	NON-COMPETING CONTINUATION	$824,056
														Subtotal = $824,056

Issue Date FY: 2022 ( Subtotal = $817,399 )
2022	2022	THE JACKSON LABORATORY	600 MAIN ST	BAR HARBOR	ME	04609	HANCOCK	USA	Drug Use and Addiction Research Programs	000	2	6/16/2022	NON-COMPETING CONTINUATION	$817,399
														Subtotal = $817,399

Issue Date FY: 2021 ( Subtotal = $832,176 )
2021	2021	THE JACKSON LABORATORY	600 MAIN ST	BAR HARBOR	ME	04609	HANCOCK	USA	Drug Use and Addiction Research Programs	000	1	8/10/2021	NEW	$832,176
														Subtotal = $832,176

Grand Total All Awards = $4,218,988

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Establishment and Characterization of Novel Mutant Mouse Models for the Addiction Research Community

Award Number: U01DA051235

ORGANIZATION: NATIONAL INSTITUTE ON DRUG ABUSE

OPDIV: NIH

AWARD CLASS: COOPERATIVE AGREEMENT

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

PERIOD OF PERFORMANCE START DATE: 08/15/2021

PERIOD OF PERFORMANCE END DATE: 05/31/2026

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