# Elucidating Regulatory Mechanisms of Lamin B1 Expression in Autosomal Dominant Leukodystrophy

> **NIH NIH R01** · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · 2024 · $439,772

## Abstract

Abstract
Autosomal Dominant Leukodystrophy (ADLD) is a fatal, adult onset, progressive neurological disease that is
characterized by widespread CNS demyelination. Most cases of ADLD are caused by tandem genomic
duplications (ADLD-dup) involving the lamin B1 gene (LMNB1) while a small subset is caused by genomic
deletions upstream of LMNB1 (ADLD-del). Both these mutations are thought to cause increased CNS LMNB1
expression and are a 100% penetrant i.e., all individuals with the mutation develop the disease. LMNB1 is a
component of the nuclear lamina and plays a critical role in maintaining nuclear architecture, regulating gene
expression and modulating chromatin positioning. Why increased expression of a widely-expressed gene such
as LMNB1 causes such a specific demyelination disorder is unknown.
Using a combination of patient data, murine and human derived oligodendrocyte (OL) lineage cells we propose
to test the hypothesis that genomic rearrangements involving Lamin B1 that cause ADLD result in mis-expression
of the lamin B1 gene. We will identify regulatory elements and mechanisms that can potentially regulate Lamin
B1 expression both in vitro and in vivo using a novel mouse model.
The experiments we have proposed will allow us to comprehensively characterize a potentially novel OL
regulatory element that can provide mechanistic insights into the tissue type specificity of ADLD and the role of
non-coding regulatory elements in OL function and demyelinating diseases.

## Key facts

- **NIH application ID:** 10756570
- **Project number:** 5R01NS126193-02
- **Recipient organization:** UNIVERSITY OF PITTSBURGH AT PITTSBURGH
- **Principal Investigator:** Quasar S Padiath
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $439,772
- **Award type:** 5
- **Project period:** 2023-01-01 → 2027-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10756570

## Citation

> US National Institutes of Health, RePORTER application 10756570, Elucidating Regulatory Mechanisms of Lamin B1 Expression in Autosomal Dominant Leukodystrophy (5R01NS126193-02). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10756570. Licensed CC0.

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