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Study of NEXMIF mosaic expression on neuronal development and connectivity in female mice

Award Number: R21MH133014
ORGANIZATION: NATIONAL INSTITUTE OF MENTAL HEALTH
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 02/06/2023
PERIOD OF PERFORMANCE END DATE: 01/31/2026

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Study of NEXMIF mosaic expression on neuronal development and connectivity in female mice - Abstract (Revised) NEXMIF is an X-linked gene with little known biological functions. Deletion of NEXMIF in humans results in encephalopathy demonstrating delayed brain development, impairments in communication and memory, intellectual disability and seizures. In females, heterozygous expression of NEXMIF due to X chromosome inactivation results in a unique pattern of NEXMIF expression in the brain, leading to complex patterns of neural connections. In this grant, we propose to utilize female mice to determine the features of mosaic expression of NEXMIF in the brain within various brain regions. We plan to cross the NEXMIF heterozygous mouse with wildtype mouse line that contains X-linked GFP, which will allow for easy visualization of the NEXMIF identities of neurons for analysis. We aim to elucidate the cellular and molecular dysregulations in the haploinsufficient female mouse brain, including neuronal morphology, synaptic protein expression, and input-specific alterations in synaptic transmission between the WT and KO neurons. Further, we find that neurons in the female transgenic brain are affected in a non-cell-autonomous manner; thus, we will examine the mechanisms by which the WT neurons are regulated by the KO cells in the mosaic neuronal population. Findings from this study will provide important original knowledge on the neurobiological function of NEXMIF, which will help with the development of strategies for clinical intervention in NEXMIF-related disorders.


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: 2024 ( Subtotal = $247,500 )
2024	2024	TRUSTEES OF BOSTON UNIVERSITY	1 SILBER WAY	BOSTON	MA	02215	SUFFOLK	USA	Mental Health Research Grants	001	2	8/14/2024	NON-COMPETING CONTINUATION	$24,750
2024	2024	TRUSTEES OF BOSTON UNIVERSITY	1 SILBER WAY	BOSTON	MA	02215	SUFFOLK	USA	Mental Health Research Grants	000	2	12/22/2023	NON-COMPETING CONTINUATION	$222,750
														Subtotal = $247,500

Issue Date FY: 2023 ( Subtotal = $206,250 )
2023	2023	TRUSTEES OF BOSTON UNIVERSITY	1 SILBER WAY	BOSTON	MA	02215	SUFFOLK	USA	Mental Health Research Grants	000	1	2/6/2023	NEW	$206,250
														Subtotal = $206,250

Grand Total All Awards = $453,750

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Study of NEXMIF mosaic expression on neuronal development and connectivity in female mice

Award Number: R21MH133014

ORGANIZATION: NATIONAL INSTITUTE OF MENTAL HEALTH

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 02/06/2023

PERIOD OF PERFORMANCE END DATE: 01/31/2026

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