# Analysis of Congenital Hydrocephalus Genes in Xenopus

> **NIH NIH R01** · YALE UNIVERSITY · 2024 · $439,851

## Abstract

Project Summary
Congenital Hydrocephalus (CH), the pathological expansion of the cerebral ventricles due to cerebrospinal fluid
(CSF) accumulation, is a common birth defect affecting 1 in every 1000 births, with high mortality and morbidity.
Treatment options are limited to surgery, which has a 50% failure rate. The lack of treatment modalities is, in
part, due to our incomplete understanding of hydrocephalus pathogenesis. Current human genetics studies
identified novel candidate genes (SMARCC1, TRIM71, PTCH1, SHH) in patients with CH. Despite their known
roles in neural stem cells, their role in hydrocephalus pathogenesis is unknown. In this work, we will use the frog
Xenopus model system to understand the underlying pathogenesis. Our recent work paired optical coherence
tomography imaging (OCT) and CRISPR/CAS9 system with the frog Xenopus to model human congenital
hydrocephalus. We demonstrated that OCT imaging of mutant tadpoles could readily detect hallmarks of human
hydrocephalus, including aqueductal stenosis and ventriculomegaly. Importantly Xenopus, as a model system,
can rapidly evaluate CH candidate genes and distinguish communicating vs. non-communicating pathogenesis
mechanisms. Our central hypothesis is that the pathogenesis of CH due to different genetic backgrounds will be
discretely different for ventricular morphology, CSF flow network, and neural progenitor cell fate, which can have
important implications for treatment. Overall, our goal is to shed light on the mechanism of hydrocephalus
pathogenesis to identify novel targets for medical management options.

## Key facts

- **NIH application ID:** 10845383
- **Project number:** 5R01NS127879-03
- **Recipient organization:** YALE UNIVERSITY
- **Principal Investigator:** ENGIN DENIZ
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $439,851
- **Award type:** 5
- **Project period:** 2022-06-01 → 2027-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10845383

## Citation

> US National Institutes of Health, RePORTER application 10845383, Analysis of Congenital Hydrocephalus Genes in Xenopus (5R01NS127879-03). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10845383. Licensed CC0.

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