# The Role of Ninein in Ethanol Anxiolysis

> **NIH NIH F31** · VIRGINIA COMMONWEALTH UNIVERSITY · 2024 · $42,911

## Abstract

Project Summary/ Abstract
Alcohol Use Disorder (AUD) is a complex disease influenced by both genetic variability and multiple
environmental factors. In the population, anxiety and stress are thought to be important drivers of alcohol
consumption, with ethanol’s anxiolytic properties suggested as contributing to progressive increases in alcohol
consumption and relapse. While there are foundations for genetic underpinnings of both AUD and anxiety
disorders, there is little evidence to define and support the genetic variability in the mechanisms driving ethanol’s
efficacy as an anxiolytic. The Miles laboratory has published a prior study, using recombinant inbred BXD mouse
strains, demonstrating a robust quantitative trait locus (QTL) underlying acute ethanol anxiolysis [3]. From this
QTL, Ninein (Nin) was implicated as a strong candidate quantitative trait gene driving variation in the anxiolytic-
like response to ethanol in the light-dark transition model of anxiety [7]. Ninein is a microtubule associated protein
(MAP) located in the centrosome and cytoplasm that anchors the minus ends of microtubules and has been
implicated in axonal growth and branching [6] Ninein has been shown to interact with Gsk3b, a known ethanol-
responsive gene implicated in synaptic plasticity and neurotransmitter trafficking that the Miles laboratory has
shown to modulate ethanol consumption [28]. Alternative splicing variants and exon-specific associated changes
in microtubule dynamics in neurons implicate that variability in Nin genomic sequence could drive genetic
variation in behavioral responses to anxiety and ethanol. This project will examine the role of Nin and Nin
transcript variant expression in basal anxiety, ethanol-induced anxiolytic-like activity and ethanol consumption
using a regulated Nin knockout model, brain region selective viral vector gene delivery and CRISPR/Cas9 exon-
skiping analysis. These objectives will be approached via the following specific aims: 1) Characterize role of
region-specific Nin on ethanol-related behaviors in C57BL/6J (B6) mice using a tamoxifen induced knockout. 2)
Characterize the role of alternative splicing of Ninein on ethanol and anxiety-related behaviors of C57BL/6J (B6)
mice, using CRISPR/Cas9 viral vectors in exon-specific deletions.

## Key facts

- **NIH application ID:** 10898837
- **Project number:** 5F31AA030727-03
- **Recipient organization:** VIRGINIA COMMONWEALTH UNIVERSITY
- **Principal Investigator:** Emma Gnatowski
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $42,911
- **Award type:** 5
- **Project period:** 2022-09-25 → 2025-09-24

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10898837

## Citation

> US National Institutes of Health, RePORTER application 10898837, The Role of Ninein in Ethanol Anxiolysis (5F31AA030727-03). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10898837. Licensed CC0.

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