title: Auditory function associated with Col11a1 haploinsufficiency in chondrodysplasia (cho) mice.
abstract: 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.
authors.affiliation: Hearing Section, National Institute on Deafness and Other Communication Disorders, National Institutes of Health, 5 Research Court, Rockville, MD 20850, USA.
authors.forename: Yvonne M
authors.initials: YM
authors.lastname: Szymko-Bennett
authors.forename: Kiyoto
authors.initials: K
authors.lastname: Kurima
authors.forename: Bjorn
authors.initials: B
authors.lastname: Olsen
authors.forename: Robert
authors.initials: R
authors.lastname: Seegmiller
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Griffith
mesh_terms: D000161:Acoustic Stimulation; D000818:Animals; D001309:Auditory Threshold; D024161:Collagen Type XI / Q000235:genetics*; D016057:Evoked Potentials, Auditory, Brain Stem; D006309:Hearing; D051379:Mice; D008810:Mice, Inbred C57BL; D010009:Osteochondrodysplasias / Q000235:genetics* / Q000503:physiopathology*
chemical_list: D024161:Collagen Type XI