# The critical ciliary role of ARL13B in kidney cystogenesis

> **NIH NIH F32** · EMORY UNIVERSITY · 2022 · $74,302

## Abstract

PROJECT SUMMARY
Polycystic kidney disease (PKD) is a chronic, progressive disease in which the kidneys accumulate fluid filled
sacs or cysts that lead to loss of kidney function, culminating in end stage renal disease and even death. PKD
affects an estimated 140,000 Americans and has an associated economic burden in excess of $7 billion
annually. An estimated 95% of PKD cases are caused by mutations in PKD1 or PKD2, which encode the cilia-
localized polycystin proteins, PC1 and PC2. In PKD mouse models, loss of renal primary cilia also results in
cyst formation. PC1 and PC2 form a complex that localizes to the primary cilia where it inhibits a cilia-
dependent cyst activation (CDCA) pathway, yet the driving force behind this CDCA pathway remains unknown.
Recent mouse models indicate that the cilia-associated protein TULP3 traffics both the unknown driver(s) of
the CDCA and the inhibitor of the CDCA (PC1/2) to the primary cilium. ARL13B is a ciliary GTPase, and its
ciliary localization requires TULP3 in the kidney (but not other tissues examined), making it an excellent
candidate as a regulator of the CDCA. In the clinic, mutations in ARL13B underlie a debilitating ciliopathy
known as Joubert Syndrome, which also presents with renal cysts. Arl13b-null mice are embryonic lethal, while
kidney-specific loss of Arl13b results in renal cysts and a loss of cilia, making it impossible to determine
whether loss of ARL13B or loss of cilia resulted in cystogenesis. Our lab recently used CRISPR to generate a
cilia-excluded Arl13b mutant mouse, V358A, which develops normally. Cilia-excluded Arl13bV358A mice exhibit
renal cysts, suggesting ARL13B plays a critical ciliary role in regulating renal cystogenesis. Delineating ciliary
signaling pathways in vivo is exceptionally challenging with current genetic models as loss of cilia ablates all
ciliary signaling, while genetic deletion of ciliary proteins removes both ciliary and cellular pools. To address
these gaps in knowledge and provide insight into how ciliary ARL13B regulates renal cystogenesis, I will use
our cilia-excluded Arl13bV358A mouse model. Because the kidney provides a unique context for ciliary signaling,
especially ARL13B signaling, the kidney is the only tissue in which to gain a better understanding of ARL13B’s
ciliary signaling in vivo. The long-term goal of this proposal is to understand ciliary ARL13B’s regulation of
kidney cystogenesis. I will test my central hypothesis that ciliary ARL13B plays a critical role in regulating
kidney cystogenesis through two complementary aims. In Aim 1, I will define the ciliary and cellular
contributions of ARL13B to kidney cystogenesis through extensive morphological and molecular phenotyping
as well as candidate and discovery-based approaches. In Aim 2, I will determine whether ciliary ARL13B
regulates the CDCA pathway. Successful completion of these aims will (1) reveal ARL13B’s ciliary function in
kidney cystogenesis, (2) identify downstream molecular r...

## Key facts

- **NIH application ID:** 10485965
- **Project number:** 5F32DK127848-03
- **Recipient organization:** EMORY UNIVERSITY
- **Principal Investigator:** Robert E Van Sciver
- **Activity code:** F32 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $74,302
- **Award type:** 5
- **Project period:** 2020-09-30 → 2024-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10485965

## Citation

> US National Institutes of Health, RePORTER application 10485965, The critical ciliary role of ARL13B in kidney cystogenesis (5F32DK127848-03). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10485965. Licensed CC0.

---

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