# Identification of ARHL Genes and their Molecular and Functional Modifiers

> **NIH NIH P01** · UNIVERSITY OF NEVADA RENO · 2020 · $377,786

## Abstract

PROJECT SUMMARY/ABSTRACT
The claudin family is composed of transmembrane proteins that are an essential part of the tight junctions
forming barriers in epithelial and endothelial tissue. In the cochlea, Claudin 9 (Cldn9) is highly expressed in
the tight junctions of the organ of Corti, where separation of high potassium (K+) endolymph from the low K+
perilymph fluid is necessary for protection of the outer hair cells (OHCs), as well as for maintaining the
Endocochlear Potential (EP) (Nakano et al 2009, Wangemann and Schacht, 1996).
Our lab has focused on identifying genes that are resistant to noise stress (Street, et al. 2014). Among the five
quantitative trait loci (QTL) that appeared in the 129S6/SvEvTac (129S6) strain, the strongest QTL contains
Cldn9. Surprisingly, when we started to study the noise sensitivity it became apparent that this locus also
displayed an age-related hearing loss (AHL) phenotype that was non-progressive hearing loss (NPHL), and a
significant mid-frequency ARHL by 12 months.
To explore functional attributes of Cldn9, we have recently developed a Doxycyline (dox) regulated version of
the Cldn9 gene that can be up or down regulated. We are assured that the changes that we observe after dox
manipulation are due to the Cldn9 expression. Here we will examine the role of Cldn9 in an aging auditory
system, including the influence noise and the question of Cldn9’s role in potassium leakage.

## Key facts

- **NIH application ID:** 9969305
- **Project number:** 5P01AG051443-05
- **Recipient organization:** UNIVERSITY OF NEVADA RENO
- **Principal Investigator:** BRUCE L TEMPEL
- **Activity code:** P01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $377,786
- **Award type:** 5
- **Project period:** — → 2023-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9969305

## Citation

> US National Institutes of Health, RePORTER application 9969305, Identification of ARHL Genes and their Molecular and Functional Modifiers (5P01AG051443-05). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9969305. Licensed CC0.

---

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