# Role of Slc25a32 and Its Interaction with Lrp6 in the Etiology of Neural Tube Defects

> **NIH NIH R01** · BAYLOR COLLEGE OF MEDICINE · 2020 · $588,122

## Abstract

ABSTRACT
Neural tube defects (NTDs) are the second most common type of structural birth defects in humans, resulting
from the failure of neural tube closure (NTC) during neurulation. The etiology of NTDs are known to be multi-
factorial, including interacting genetic and environmental factors. There are multiple developmentally-related
signaling pathways involved as NTC proceeds spatially and temporally. The identification of specific genetic
variants that contribute significantly to the etiology of NTDs, and the characterization of their underlying molecular
and cellular mechanisms leading to failed NTC has progressed slowly over the last several decades. What is
important to recognize is that NTDs stand out as a preventable birth defect. Research spanning decades
demonstrates that maternal periconceptional supplementation with folic acid can reduce the risk of NTDs by 30%
to 70%. Yet not all NTDs are folate responsive. Currently between 30-50% of all NTDs are not preventable by
folic acid supplementation. The proposed research project is based on our recently published folic acid non-
responsive Slc25a32 null mouse model, and its interaction with a folic acid responsive Wnt co-receptor, Lrp6
mutant mouse model. The studies are designed to help elucidate the underlying mechanisms characteristic of
folic acid resistant NTDs, and to test our hypothesis that these folate resistant NTDs may be prevented by
interventions with downstream folate metabolites, such as formate. It was recently determined that formate could
rescue folic acid-resistant NTD mice, suggesting that mitochondrial one carbon metabolism might be
compromised in the non-folate responsive NTD population. Despite almost 40 years of intensive study, we still
do not fully understand the molecular, cellular and biochemical mechanisms that underlie the folate-dependent
process of NTC. This gap in our knowledge hinders our ability to make informed health policy decisions about
folate fortification and to identify novel treatments to prevent folate-resistant NTDs.

## Key facts

- **NIH application ID:** 9863282
- **Project number:** 1R01HD100535-01
- **Recipient organization:** BAYLOR COLLEGE OF MEDICINE
- **Principal Investigator:** RICHARD H. FINNELL
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $588,122
- **Award type:** 1
- **Project period:** 2020-03-10 → 2025-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9863282

## Citation

> US National Institutes of Health, RePORTER application 9863282, Role of Slc25a32 and Its Interaction with Lrp6 in the Etiology of Neural Tube Defects (1R01HD100535-01). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9863282. Licensed CC0.

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