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Novel mouse models to dissect the role of genetics, sex, and environment in heterogeneous outcomes in CNS autoimmune disease

Award Number: R01AI172166
ORGANIZATION: NATIONAL INSTITUTE OF ALLERGY & INFECTIOUS DISEASES
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 08/09/2022
PERIOD OF PERFORMANCE END DATE: 07/31/2027

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Novel mouse models to dissect the role of genetics, sex, and environment in heterogeneous outcomes in CNS autoimmune disease - PROJECT ABSTRACT/SUMMARY Multiple sclerosis (MS) is a chronic disease that is the leading cause of non-traumatic neurological disability in young adults. The disease is caused by an aberrant immune-mediated attack on the central nervous system, which causes tissue destruction and subsequent neurologic disability. Disease course varies greatly from individual to individual, from relapsing-remitting MS, to primary progressive MS, the latter highly debilitating and refractory to treatment. MS is three times more common in women, but tends to be more severe in men. MS has a significant heritable component, with up to 30% of the disease risk being genetically determined. While recent studies have identified candidate genes that are associated with MS risk, it remains unclear how these genes work and whether these are truly causative. Additionally, it is completely unknown why some individuals get different forms of this disease, and why there are differences between men and women. The other 70% of disease risk comes from environment or gene-by-environment interactions, representing an attractive avenue for presentation. However, how risk factors, in particular chronic gammaherpes virus infection, mechanistically impact MS risk or progression is unclear. These types of questions are very difficult, if not impossible, to address in studies in humans, and in this application, we propose to use animal models of MS. Mouse models offer powerful genetic tools, and allow for cause/effect mechanistic studies, but conventional mouse models are highly artificial and lack genetic diversity. We will use several novel mouse genetic models that are designed to better represent the complex genetic structure of human populations, which will allow us to dissect the complex genetic architecture underlying MS pathogenesis, to identify specific genes responsible for various poorly understood aspects of this disease, and to identify gene-by-environment interactions and novel mechanisms underlying environmental risk factors.


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: 2026 ( Subtotal = $521,143 )
2026	2026	UNIVERSITY OF VERMONT & STATE AGRICULTURAL COLLEGE	85 S PROSPECT STREET	BURLINGTON	VT	05405	CHITTENDEN	USA	Allergy and Infectious Diseases Research	000	5	6/30/2026	NON-COMPETING CONTINUATION	$521,143
														Subtotal = $521,143

Issue Date FY: 2025 ( Subtotal = $521,143 )
2025	2025	UNIVERSITY OF VERMONT & STATE AGRICULTURAL COLLEGE	85 S PROSPECT STREET	BURLINGTON	VT	05405	CHITTENDEN	USA	Allergy and Infectious Diseases Research	000	4	7/7/2025	NON-COMPETING CONTINUATION	$521,143
														Subtotal = $521,143

Issue Date FY: 2024 ( Subtotal = $521,143 )
2024	2024	UNIVERSITY OF VERMONT & STATE AGRICULTURAL COLLEGE	85 S PROSPECT STREET	BURLINGTON	VT	05405	CHITTENDEN	USA	Allergy and Infectious Diseases Research	000	3	7/24/2024	NON-COMPETING CONTINUATION	$521,143
														Subtotal = $521,143

Issue Date FY: 2023 ( Subtotal = $521,143 )
2023	2023	UNIVERSITY OF VERMONT & STATE AGRICULTURAL COLLEGE	85 S PROSPECT STREET	BURLINGTON	VT	05405	CHITTENDEN	USA	Allergy and Infectious Diseases Research	000	2	7/7/2023	NON-COMPETING CONTINUATION	$521,143
														Subtotal = $521,143

Issue Date FY: 2022 ( Subtotal = $516,463 )
2022	2022	UNIVERSITY OF VERMONT & STATE AGRICULTURAL COLLEGE	85 S PROSPECT ST	BURLINGTON	VT	05405	CHITTENDEN	USA	Allergy and Infectious Diseases Research	000	1	8/9/2022	NEW	$516,463
														Subtotal = $516,463

Grand Total All Awards = $2,601,035

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Novel mouse models to dissect the role of genetics, sex, and environment in heterogeneous outcomes in CNS autoimmune disease

Award Number: R01AI172166

ORGANIZATION: NATIONAL INSTITUTE OF ALLERGY & INFECTIOUS DISEASES

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 08/09/2022

PERIOD OF PERFORMANCE END DATE: 07/31/2027

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