# Examining Progression of a Neurodegenerative Disorder

> **NIH NIH R03** · UNIVERSITY OF TENNESSEE HEALTH SCI CTR · 2020 · $152,000

## Abstract

There is a fundamental gap in understanding how the underlying mutation leads to a recently identified disease
called UBTF E210K Neuroregression Syndrome (UNS), a debilitating neurodevelopmental disorder. UNS is
associated with a variant of UBTF, a transcriptional regulatory protein, in which glutamic acid at reside 210 is
mutated to a lysine (E210K). The onset of UNS is about 2.5 to 3 years of age. In order to study UNS,
we have generated a UBTF+/E210K mouse as a novel animal model of this disease. Increased comprehension of
disease progression will identify the pathways and molecules that could serve the role of potential therapeutic
targets. The long-term goal is to develop therapeutic intervention that decrease morbidity of this devastating
illness. The objective in this application is to examine the histopathology of the brain in UBTF+/E210K and
UBTFE210K/E210K mice at different ages, and the gene expression profiles in the cerebellum and cortex of WT
and UBTF+/E210K mice. The central hypothesis is that increased levels of DNA damage and apoptosis will
correlate with sensorimotor, behavioral and neurological phenotypes. The experiments in this proposal will be
guided by two Specific Aims: 1) Examine and compare the histopathology and gene expression profile of
brains from UBTF+/+ (wild-type), UBTF+/E210K, and UBTFE210K/E210K mice during disease progression. and
2) Identify the brain regions and cell populations implicated in sensorimotor and cognitive dysfunction.
In the first aim, cellular characteristics such as DNA damage, apoptosis and gene expression profile will be
monitored in brains from wild-type and mutant mice at different ages. In the second aim, we will identify the
brain regions and vulnerable cell populations and corelate with behavioral abnormalities. The approach is
innovative because disease progression of UNS is poorly understood and we take advantage of a novel mouse
model to overcome the issues with performing these experiments in a human system. The proposed research
is significant because it is expected to substantially advance our understanding of disease progression and
identify potential pathways and molecules that are the most likely targets of disease modifying intervention for
the debilitating UTBF E210K Neuroregression Syndrome.

## Key facts

- **NIH application ID:** 10056517
- **Project number:** 1R03NS114616-01A1
- **Recipient organization:** UNIVERSITY OF TENNESSEE HEALTH SCI CTR
- **Principal Investigator:** Mohammad Moshahid Khan
- **Activity code:** R03 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $152,000
- **Award type:** 1
- **Project period:** 2020-09-15 → 2023-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10056517

## Citation

> US National Institutes of Health, RePORTER application 10056517, Examining Progression of a Neurodegenerative Disorder (1R03NS114616-01A1). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10056517. Licensed CC0.

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