# Studies on Pol III-Associated Leukodystrophy

> **NIH NIH R21** · ALBERT EINSTEIN COLLEGE OF MEDICINE · 2020 · $208,750

## Abstract

Project Summary
 Pol III-associated leukodystrophy is an autosomal recessive neurodegenerative disease linked to mutations
in subunits of RNA polymerase III (Pol III). The clinical and radiologic spectrum of the disorder has only
recently been defined. Pol III-associated leukodystrophy is characterized by hypomyelination of cerebral white
matter and presents as a progressive decline in motor function, developmental delay and intellectual disability.
Disease onset typically occurs during childhood but the age range at diagnosis is broad, reflecting the variable
severity and slow progression of the disease. Other clinical characteristics include myopia, hypodontia and
endocrine abnormalities but these features are not always present. The mechanism of pathogenesis is
unknown and no therapeutic options are available. Further progress in understanding this disease is limited by
the lack of model systems. Thus, the goal of this research is to develop a mouse model of Pol III-associated
leukodystrophy. We have created a knock-in mouse expressing clinically-defined Pol III-associated
leukodystrophy mutations. We will characterize the behavioral, radiologic and neuropathologic phenotypes of
these mice. Phenotypic changes will be correlated with the impact of the mutation on Pol III transcription, tRNA
biogenesis and protein synthesis. In addition, we will test a model for genetic suppression of Pol III-associated
leukodystrophy phenotypes. These studies will significantly enhance understanding of the pathogenesis of Pol
III-associated leukodystrophy and will provide a model system for testing therapeutic approaches targeting the
disease.

## Key facts

- **NIH application ID:** 10076558
- **Project number:** 5R21HD097557-02
- **Recipient organization:** ALBERT EINSTEIN COLLEGE OF MEDICINE
- **Principal Investigator:** Robyn Moir
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $208,750
- **Award type:** 5
- **Project period:** 2019-03-01 → 2021-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10076558

## Citation

> US National Institutes of Health, RePORTER application 10076558, Studies on Pol III-Associated Leukodystrophy (5R21HD097557-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10076558. Licensed CC0.

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