# Measuring kidney NaCl transport in vivo with genetically encoded sensors

> **NIH NIH R21** · WAYNE STATE UNIVERSITY · 2024 · $400,820

## Abstract

Abstract
Nephron salt reabsorption is essential to salt and water homeostasis and its dysregulation is involved in the
progression of kidney and cardiovascular diseases, including chronic kidney disease, hypertension and those
started by diabetes and obesity. There are only a few methods to measure renal tubular ion transport at the
single cell in live animals that were developed over 40 years ago. Using multi-photon imaging of the live mouse
kidney we recently developed a method to monitor Thick Ascending Limb (TAL)-mediated urine concentration at
the single tubule level. We propose to develop 2 transgenic mice lines expressing a Chloride-sensing genetically
encoded probe that will allow measurement of cortical TAL and Distal Convoluted tubule (DCT) NaCl transport
using 2-photon microcopy. In Specific Aim 1 we will generate inducible Umod-Cre, Slc12a3-Cre-SuperClomelen
expressing transgenic mice that will allow the methodological development of NaCl transport measurements in
vivo. In specific Aim 2, we will develop a method to measure NKCC2 and NCC activity in live mice by monitoring
the initial rates of Cl entry using SuperClomeleon mice or ClopHensor expression in the distal tubule in vivo. Our
preliminary data demonstrate the use of a ratiometric Cl-sensitive probe to measure intracellular chloride in
epithelial cells and measurement of urinary concentrating capacity and luminal Na via intravital MP microscopy
in mice. Our studies will demonstrate the use of genetically encoded Cl indicators for measurement of nephron
NaCl transport and spur the development of new sensors (K, Na, Mg, cAMP, cGMP, etc) to be used in live mice.

## Key facts

- **NIH application ID:** 11035602
- **Project number:** 1R21DK142082-01
- **Recipient organization:** WAYNE STATE UNIVERSITY
- **Principal Investigator:** Pablo A. Ortiz
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $400,820
- **Award type:** 1
- **Project period:** 2024-09-06 → 2026-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/11035602

## Citation

> US National Institutes of Health, RePORTER application 11035602, Measuring kidney NaCl transport in vivo with genetically encoded sensors (1R21DK142082-01). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/11035602. Licensed CC0.

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