# Ablating choroid plexus epithelial cells in the developing mouse brain: A new tool to approach CSF disorders

> **NIH NIH R21** · UNIVERSITY OF CINCINNATI · 2022 · $456,877

## Abstract

Project Summary
The choroid plexus (CP) and cerebral spinal fluid (CSF) system serve multiple active roles in regulating brain
formation and the brain's overall health. Emerging new knowledge is determining catalogs of molecules in the
CP-CSF system and their role in brain development as well as an immune-brain interaction. Dysregulation of
CSF production or circulation causes diseases such as hydrocephalus, and CP atrophy has been observed
in multiple CNS disorders. These observations in the human brain disorders indicate that the CP-CSF system
has engaged roles in the brain disease progression or exacerbation. There is rising interest in CP-targeted
therapies in CSF volume and neuroinflammation management. In fact, recently, clinical benefits of CP
coagulation in endoscopic third ventriculostomy treatment have been demonstrated in the treatment of
pediatric hydrocephalus patients in developing countries. However, contrary to its important roles, the CP-
CSF system has mainly been remained an under-explored field in neuroscience due to limitations in the
number of available tools to precisely modulate its functions.
The NIH Funding Opportunity PA-21-219 " The Joint NINDS/NIMH Exploratory Neuroscience Research Grant
program" recognizes the unmet need for "novel tools or models that have the potential to bring breakthroughs
to the neuroscience community." By using a novel transgenic mouse line that we recently discovered, our
project will address the goals by (1) establishing a new tool to ablate CP in mice and (2) modeling
hydrocephalus brains with CP-targeted treatment. Our rigorous preliminary data indicated that (1) this line
can induce exclusive apoptotic cell death only in the CP epithelial cells and (2) the CP ablation results in
partial to near-complete 50-90% reduction in ventricular volume depending on the dose and timing of agent
administration. We will characterize the dosing effects and investigate the positive and potential adverse
effects of partial and near-complete CP ablation in hydrocephalus and otherwise healthy brain development.
Our comprehensive MRI, intracranial pressure, gene expression, cytokine profiling, and immunohistochemical
characterization will reveal the effects of this new tool on intracranial pressure, ventricle size, CP regeneration
capacity, and postnatal neurodevelopment. This will broaden our fundamental understanding of the function
of CP and CSF in perinatal brain development. In addition, our needs-based tools will be important in clarifying
the key role of the CP-CSF system in the pathogenesis and treatment of hydrocephalus.
This project provides an essential platform for elucidating the role of CP-CSF in underlying brain development
and function. By establishing a new tool to remove CP-CSF in mice at any desired timepoints (neonatal to
adulthood), our project will make significant contributions and impact on promoting studies of the CP-CSF
system in a wide range of topics in neuroscience and brain disea...

## Key facts

- **NIH application ID:** 10605760
- **Project number:** 1R21NS127177-01A1
- **Recipient organization:** UNIVERSITY OF CINCINNATI
- **Principal Investigator:** JUNE GOTO
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $456,877
- **Award type:** 1
- **Project period:** 2022-09-26 → 2024-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10605760

## Citation

> US National Institutes of Health, RePORTER application 10605760, Ablating choroid plexus epithelial cells in the developing mouse brain: A new tool to approach CSF disorders (1R21NS127177-01A1). Retrieved via AI Analytics 2026-05-28 from https://api.ai-analytics.org/grant/nih/10605760. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*