# Characterization of a Novel Ataxia Phenotype

> **NIH NIH F31** · NORTHWESTERN UNIVERSITY · 2024 · $22,613

## Abstract

PROJECT SUMMARY/ABSTRACT
Defining genetic variation responsible for neuromuscular phenotypes has provide insight about basic
neurological mechanisms as well as insight on human disease mechanisms. Mouse models have also been
used to understand genetic mechanisms that cause relevant neurological conditions. These discoveries were
made through the classic genetic approach of characterizing a phenotype and then defining the genotype that
accounts for that defect. This approach has been instrumental for a host of discoveries resulting in a more
thorough understanding of underlying mechanisms of disease. The project put forth under this proposal follows
a similar approach. We seek to identify and characterize a potentially novel variant responsible for a severe,
“novel ataxia phenotype” (nap) discovered in our lab with the ultimate goal of shedding light on novel
mechanisms underlying ataxia. This proposal outlines experiments to characterize the affected tissue type and
evaluate whole genome sequencing (WGS) and RNA sequencing to isolate potentially causal genetic variants
to experimentally validate. This approach ensures that progress is not wholly dependent on a specific result,
rather several experiments can be done in concert that will increase the probability of success. Our approach
of utilizing WGS will providing the genetic landscape thereby elucidating potential noncoding variants that may
elicit the phenotype in the nap mice. After determining which tissue type is affected, we will perform RNA
sequencing to elucidate transcriptomic differences in the nap mice to provide potential mechanisms underlying
the phenotype. Successfully identifying the variant through computationally analysis and experimental
validation will allow for further experiments to better understand the mechanism of action of the variant, as
outlined in the aims. Given the presentation of the ataxia phenotype, we suspect the primary tissue affected
will be the cerebellum and/or brainstem and through breeding, we have established that this variant is inherited
in an autosomal recessive pattern. Through preliminary genome analysis, we have identified several novel
candidates and excluded several known genes responsible for ataxia phenotypes. The results of this project
are expected to provide further insight into the molecular mechanisms that underlie ataxia and will potentially
serve as a model for therapeutic development to ameliorate ataxia symptomology. This project was designed
to expand the skills and training of the principal investigator with the goal of comprehensive training in
bioinformatics and characterization of the mouse model.

## Key facts

- **NIH application ID:** 10818412
- **Project number:** 5F31NS122495-04
- **Recipient organization:** NORTHWESTERN UNIVERSITY
- **Principal Investigator:** Alexander Telenson
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $22,613
- **Award type:** 5
- **Project period:** 2021-04-01 → 2024-09-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10818412

## Citation

> US National Institutes of Health, RePORTER application 10818412, Characterization of a Novel Ataxia Phenotype (5F31NS122495-04). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10818412. Licensed CC0.

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