# Role of Phox2b in mouse respiratory chemoreceptor neurons

> **NIH NIH R03** · UNIVERSITY OF VIRGINIA · 2024 · $161,500

## Abstract

PROJECT SUMMARY
Congenital central hypoventilation syndrome (CCHS) is an autonomic and respiratory disorder caused by
mutations in the paired-like homeobox transcription factor gene, PHOX2B. CCHS patients have severe
episodes of hypoventilation, especially during sleep, that likely reflect reduced arousal and ventilatory
responses to high CO2. In CCHS, PHOX2B mutations commonly include polyalanine repeat mutations
(PARMs), with increasing severity associated with more extensive expansions, along with other loss-of-function
gene variants that yield particularly dire clinical presentations including various accompanying dysautonomia.
The neuropathology associated with CCHS-causing mutations in humans has not been delineated. In mice,
Phox2b is expressed in several brain-stem neurons that may be relevant for various clinical features of CCHS.
However, the respiratory chemosensory neurons of the retrotrapezoid nucleus (RTN) are thought to be
particularly important for the alveolar hypoventilation and loss CO2-dependent reflexes, the two cardinal signs
of CCHS, because they are intrinsically CO2-sensitive, contribute to breathing and waking reflexes activated by
hypoventilation, and they are uniquely eliminated in mouse genetic models of CCHS. The transcriptional role
of Phox2b in RTN neurons, and how it contributes to respiratory regulation by those neurons has not been
determined. This proposal examines gene regulatory functions of wild type and polyalanine mutants of Phox2b
in RTN neurons, and the relevance of Phox2b-regulated genes for RTN function in respiratory control.

## Key facts

- **NIH application ID:** 10889648
- **Project number:** 1R03TR004719-01A1
- **Recipient organization:** UNIVERSITY OF VIRGINIA
- **Principal Investigator:** Yingtang Shi
- **Activity code:** R03 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $161,500
- **Award type:** 1
- **Project period:** 2024-03-07 → 2025-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10889648

## Citation

> US National Institutes of Health, RePORTER application 10889648, Role of Phox2b in mouse respiratory chemoreceptor neurons (1R03TR004719-01A1). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10889648. Licensed CC0.

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