# An in vivo screen for genes underlying protective neonate respiratory reflexes to identify potential contributors to Sudden Infant Death Syndrome and other congenital respiratory pathophysiologies

> **NIH NIH R01** · BAYLOR COLLEGE OF MEDICINE · 2024 · $688,785

## Abstract

PROJECT SUMMARY ABSTRACT
The goal of this proposal is to identify genes that are required for neuro-developmental and cellular processes
critical to protective neonate respiratory reflexes that may be perturbed in Sudden Infant Death Syndrome
(SIDS) and other congenital respiratory pathophysiologies. To that end, we are in a unique position to leverage
the Baylor College of Medicine (BCM) Knockout Mouse Project-2 (KOMP2)/International Mouse Phenotyping
Consortium (IMPC) efforts to knock out or mutate and characterize every gene in the mouse genome. The
BCM KOMP2/IMPC effort is focused on adult as well as some embryonic and perinatal top-level phenotyping.
However, this effort does not systematically or deeply evaluate adult or neonate respiration. Thus, we aim to
leverage the BCM KOMP2/IMPS knockout production and phenotyping pipeline to identify genes critical to the
development and function of neural networks in neonate respiration.
The hypercapnic and hypoxic ventilatory reflexes are hypothesized to be perturbed in SIDS and several other congenital
respiratory disorders. Failure of the neonate auto-resuscitation reflex is thought to be a common end point for many
SIDS cases. Therefore across two aims, we propose to screen KOMP2 mutant mouse lines to identify novel genes
involved in the development and function of protective neonate respiratory reflexes including 1) the hypercapnic and
hypoxic ventilatory reflexes; 2) and the neonate auto-resuscitation reflex; 3) followed by an initial neuro-anatomical
characterization of cellular, molecular and genetic markers in the mutants. To achieve the high throughput capacity and
precision needed to screen sufficient numbers of mutant lines and gain meaningful results, we have developed a novel
robotic closed loop automated neonate respiratory platform and data analysis pipeline.
The proposed phenotyping pipeline will enable a multifaceted characterization of genes that when homozygously or
heterozygously mutated, disrupt critical protective neonate respiratory reflexes. The successful outcomes will deliver a
suite of genes that provide a foundation for additional studies to yield important clues about the genetic, molecular,
cellular processes that underly respiratory neural network development and function in neonates as well as inform upon
the mechanistic underpinnings of congenital pathophysiologies such as SIDS, CCHS, Rett Syndrome and others.

## Key facts

- **NIH application ID:** 10746005
- **Project number:** 5R01HL161142-03
- **Recipient organization:** BAYLOR COLLEGE OF MEDICINE
- **Principal Investigator:** Russell S Ray
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $688,785
- **Award type:** 5
- **Project period:** 2021-12-01 → 2025-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10746005

## Citation

> US National Institutes of Health, RePORTER application 10746005, An in vivo screen for genes underlying protective neonate respiratory reflexes to identify potential contributors to Sudden Infant Death Syndrome and other congenital respiratory pathophysiologies (5R01HL161142-03). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10746005. Licensed CC0.

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