# Elucidating the role of Prdm12 in the development and maintenance of nociceptive neurons

> **NIH NIH F31** · UT SOUTHWESTERN MEDICAL CENTER · 2020 · $31,814

## Abstract

PROJECT SUMMARY
Painful conditions are a huge medical burden with an estimated prevalence of 32% per year and an economic
burden over $600 billion accounting for treatment and lost productivity costs. While opioids can provide analgesic
relief for some patients, their increasing use in medicine led to an epidemic of its own, with an ever-increasing
mortality rate due to overdose, highlighting the need for novel, non-opioid analgesics. Recently, research to meet
this need has been fueled by the study of mutations leading to painlessness (Congenital Insensitivity to Pain
(CIP)). As part of this effort, I have focused on a newly identified variant of CIP caused by a series of loss-of-
function mutations in the chromatin-modifying factor, PRDM12. Patients with Prdm12 mutations are unable to
detect painful (nociceptive) stimuli, without defects in other sensory modalities (touch, vibration, proprioception,
and itch). Furthermore, Prdm12 has been proposed to play a role in nociceptor development, consistent with the
finding that humans with PRDM12-associated CIP lack small diameter nociceptors responsible for transmitting
pain sensation. To better understand how Prdm12 loss-of-function leads to CIP, I developed a mouse model
of Prdm12-associated CIP to test the hypothesis that PRDM12 expression is required for the
development and maintenance of nociceptive sensory neurons. In Aim 1, I will use this model to analyze
the developmental and behavioral defects that result from Prdm12 loss-of-function mice compared to controls. I
will start by looking for differences in neurogenesis, cell type specification, or cell death in dorsal root ganglia of
Prdm12 loss-of-function mice. I will then compare these developmental changes with behavioral studies
investigating nociceptive sensation of these mice to understand how loss of particular subsets of sensory
neurons leads to defects in specific modalities of nociception. Finally, I will use mRNA-seq to begin to investigate
the mechanism of action of PRDM12 at various stages of development. In Aim 2, I will test whether PRDM12 is
involved in the maintenance of nociceptive sensory neurons. I will do this by using a tamoxifen-inducible model
to knockout Prdm12 at late embryonic to adulthood stages, and examining the DRG composition, pain behavior
phenotype, and transcriptional changes in these mice. Additionally, I will use cultured DRG neurons from these
mice to assess changes in neuronal populations and excitability using electrophysiology. Overall, the project will
provide new insight into the developmental role of Prdm12 and our understanding of pain sensation, while also
serving to open potentially new areas of analgesic discovery that could benefit both acute and chronic pain
conditions.

## Key facts

- **NIH application ID:** 10019343
- **Project number:** 5F31NS111796-02
- **Recipient organization:** UT SOUTHWESTERN MEDICAL CENTER
- **Principal Investigator:** Mark Landy
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $31,814
- **Award type:** 5
- **Project period:** 2019-08-12 → 2021-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10019343

## Citation

> US National Institutes of Health, RePORTER application 10019343, Elucidating the role of Prdm12 in the development and maintenance of nociceptive neurons (5F31NS111796-02). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10019343. Licensed CC0.

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