Auditory function associated with Col11a1 haploinsufficiency in chondrodysplasia ( cho) mice

Heterozygosity for mutations in the fibrillar collagen gene COL11A1 causes sensorineural hearing loss in patients with Stickler syndrome or Marshall syndrome. Chondrodysplasia ( cho) is a functional null allele of Col11a1 that causes lethal chondrodysplasia in cho/ cho newborn mice, and osteoarthritis in cho/+ heterozygotes. To determine if Col11a1 haploinsufficiency causes hearing loss in cho/+ mice, auditory brainstem response (ABR) thresholds were measured at 2, 4, 6, 8 and 10 months of age. There was no difference in ABR thresholds for click and tone burst stimuli between cho/+ and +/+ mice at all ages. In contrast to the conclusion of a previous report, our results indicate that Col11a1 haploinsufficiency does not cause significant hearing loss on the C57BL/6 strain background. We conclude that Stickler syndrome and Marshall syndrome mutations in COL11A1 cause hearing loss via dominant negative effects upon wild-type fibrillar collagen polypeptides in the extracellular matrices of the cochlea.