# Function and Regulation of PMP22 in CMT1A and HNPP

> **NIH NIH K22** · JOHNS HOPKINS UNIVERSITY · 2021 · $122,985

## Abstract

Project Summary/Abstract
 The fact that both duplication and deletion of the Peripheral Myelin Protein 22 (PMP22) gene cause
dysmyelinating peripheral neuropathy illustrates the importance of PMP22 for peripheral myelin integrity.
PMP22 duplication causes Charcot-Marie-Tooth Disease Type 1A (CMT1A) and PMP22 deletion causes
Hereditary Neuropathy with Liability to Pressure Palsies (HNPP). Although CMT1A and HNPP are the most
common inherited peripheral neuropathies, research on them is underfunded and there are currently no
disease-modifying treatments. This is largely due to the fact that PMP22 function and the consequence of
altered PMP22 expression remain unclear. Thus, there is a critical need to expand knowledge of what PMP22
does in myelin, how it is regulated and when precise expression is required as a means to improve therapeutic
potential of CMT1A and HNPP. This proposal aims to utilize cutting-edge techniques, including conditional
mouse models and super resolution microscopy, and knowledge of cell adhesion and membrane biophysics to
advance understanding of CMT1A and HNPP pathomechanisms. My central hypothesis is that PMP22 gene
dosage and lipid raft association govern localization and organization of myelin adherens and tight
junctions; a function that is most critical during development. In Aim 1, I will determine how PMP22
regulates adhesion junction organization in peripheral nerve myelin during development and aging with super
resolution and electron microscopy. I will aid the interpretation of these studies by evaluating the effects of
altered PMP22 expression on prototypical adherens and tight junctions in Madin-Darby Canine Kidney (MDCK)
epithelial cells. The temporal requirement for precise PMP22 expression in myelin will also be defined by
generating powerful conditional mouse models of CMT1A and HNPP. In Aim 2, I will determine how
palmitoylation impacts PMP22 lipid raft association and regulation of adhesion junctions and define the
biophysical properties of PMP22 within the plasma membrane using MDCK and Schwann cell models of
CMT1A and HNPP and advanced biophysical methods. This K22 Career Transition Award will provide me with
additional training, mentorship and expertise in cell adhesion, membrane biophysics and microscopy, thereby
enabling my proposed research and facilitating my transition to independence. This training will complement
my previous training in cell and molecular neurobiology and my current peripheral nerve training, and the
expertise acquired during Phase I will be applied to more complex models in Phase II to expand mechanistic
details. Completion of these aims will accelerate progress towards my long-term goal of developing an
independent academic research career studying pathomechanisms of CMT1A and HNPP as a means to
improve their therapeutic potential. The training and mentorship provided by this award will expand my
technical skills and expertise, positioning me for success as an independent inves...

## Key facts

- **NIH application ID:** 10350403
- **Project number:** 1K22NS125057-01
- **Recipient organization:** JOHNS HOPKINS UNIVERSITY
- **Principal Investigator:** Kathryn Renae Moss
- **Activity code:** K22 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $122,985
- **Award type:** 1
- **Project period:** 2021-09-21 → 2026-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10350403

## Citation

> US National Institutes of Health, RePORTER application 10350403, Function and Regulation of PMP22 in CMT1A and HNPP (1K22NS125057-01). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10350403. Licensed CC0.

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