RT Journal Article
SR Electronic
T1 Limiting Hearing Loss in Transgenic Mouse Models
JF eneuro
JO eNeuro
FD Society for Neuroscience
SP ENEURO.0465-24.2025
DO 10.1523/ENEURO.0465-24.2025
VO 12
IS 2
A1 Babola, Travis A.
A1 Donovan, Naomi
A1 Darcy, Sean S.
A1 Spjut, Catalina D.
A1 Kanold, Patrick O.
YR 2025
UL http://www.eneuro.org/content/12/2/ENEURO.0465-24.2025.abstract
AB Transgenic mice provide unprecedented access to manipulate and visualize neural circuits; however, those on a C57BL/6 background develop progressive hearing loss, significantly confounding systems-level and behavioral analysis. While outbreeding can limit hearing loss, it introduces strain variability and complicates the generation of complex genotypes. Here, we propose an approach to preserve hearing by crossing transgenic mice with congenic B6.CAST-Cdh23Ahl+ mice, which maintain low-threshold hearing into adulthood. Widefield and two-photon imaging of the auditory cortex revealed that 2.5-month-old C57BL/6 mice exhibit elevated thresholds to high-frequency tones and widespread cortical reorganization, with most neurons responding best to lower frequencies. In contrast, Ahl+ C57BL/6 mice exhibited robust neural responses across tested frequencies and sound levels (4–64 kHz, 30–90 dB SPL) and retained low thresholds into adulthood. Our approach offers a cost-effective solution for generating complex genotypes and facilitates more interpretable systems neuroscience research by eliminating confounding effects from hearing loss.