# Identifying Genetic Loci Associated with Neurocristopathies using the Deer Mouse, Peromyscus maniculatus

> **NIH NIH R03** · UNIVERSITY OF SOUTH CAROLINA AT COLUMBIA · 2020 · $151,058

## Abstract

Project Summary: Identifying Genetic Loci Associated with Neurocristopathies using the Deer Mouse,
Peromyscus maniculatus
The neural crest is a multipotent progenitor cell type that contributes to multiple tissues throughout the body,
including the peripheral nervous system, craniofacial tissues, the heart, and melanocytes. People with
mutations that affect neural crest development can develop neurocristopathies, a broad class of congenital
diseases that are often associated with pigmentation defects. Therefore, the rationale for this proposal is that
identifying causative mutations for pigmentation defects in deer mice, Peromyscus maniculatus, will increase
our knowledge of genetic lesions that can disrupt neural crest development and cause neurocristopathies. The
dominant spot mutation in P. maniculatus results in a white blaze on the forehead of heterozygotes and is
embryonic lethal when homozygous. The overall objective of this proposal is to capitalize on the unique
features of P. maniculatus as a model system to identify the causative mutation for dominant spot. Our
preliminary data show that dominant spot is linked to a 1.7 Mb interval on chromosome 20, which contains the
neural crest regulatory gene Sox10. Sequencing of Sox10 exons from dominant spot homozygous embryos did
not identify any sequence variants co-segregating with the phenotype, suggesting that the mutation is in a
Sox10 regulatory sequence. In addition, we have found that the size of the forehead blaze varies dependent on
the genetic background, suggesting the presence of modifier genes. These data have led to our central
hypothesis that dominant spot results from a mutation in a regulatory region of Sox10 and that modifier genes
cause variability in the dominant spot phenotype by interacting with Sox10 gene expression. This hypothesis
will be tested by pursuing two specific aims. First, we will use target enrichment and high throughput
sequencing to identify sequence variants associated with dominant spot. Second, a quantitative trait loci (QTL)
analysis will be used to identify QTLs that are associated with the variability in spot size. This proposal is
innovative because we propose to develop P. maniculatus as a model system for studying neuroscristopathies.
The results from the proposed research will be significant because identifying the causative mutation for
dominant spot and its genetic modifiers will increase our understanding of the neural crest gene regulatory
network and provide genetic loci of clinical significance for screening in human neuroscristopathies.

## Key facts

- **NIH application ID:** 9960495
- **Project number:** 5R03DE028371-02
- **Recipient organization:** UNIVERSITY OF SOUTH CAROLINA AT COLUMBIA
- **Principal Investigator:** SHANNON William DAVIS
- **Activity code:** R03 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $151,058
- **Award type:** 5
- **Project period:** 2019-07-01 → 2022-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9960495

## Citation

> US National Institutes of Health, RePORTER application 9960495, Identifying Genetic Loci Associated with Neurocristopathies using the Deer Mouse, Peromyscus maniculatus (5R03DE028371-02). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/9960495. Licensed CC0.

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