The BALB/c mouse as an animal model for progressive sensorineural hearing loss

Abstract

To develop the BALB/c mouse strain as an animal model for the study of progressive sensorineural hearing loss, mice ranging in age from young adult through middle age were studied. Auditory brainstem response thresholds, histopathology [cytocochleograms for hair cells, the packing density of spiral ganglion cells (SGCs), the number of neurons and overall size of the anterior ventral cochlear nucleus (AVCN)], and behavioral paradigms (prepulse inhibition, fear-potentiated startle) were compared with previous data from C57BL/6J (C57) and DBA/2J (DBA) mouse strains. Progressive high frequency hearing loss in BALB/c mice was generally more rapid than C57 and slower than DBA (e.g. mean thresholds for 16 kHz: 10-month-old BALB/c mice=71 dB SPL; 55-day-old DBA mice=79 dB SPL; 12-month-old C57 mice=50 dB SPL). Like the other strains, BALB/c exhibited a progressive loss of hair cells and SGCs that was most severe in the cochlear base and least severe in the middle turns; however, BALB/c mice had relatively more SGC loss in the apex. Unlike C57 and DBA, no loss of neurons was observed in the AVCN following cochlear pathology (although AVCN volume was reduced). Like the other strains, successful fear conditioning was obtained with a 12 kHz conditioned stimulus. Prepulse inhibition showed that middle and low frequency tones (4–12 kHz) became more salient as high frequency hearing declined. Similar results had been previously obtained with C57 and DBA mice and were interpreted as reflecting hearing-loss-induced plasticity in the central auditory system.