title: A novel QTL underlying early-onset, low-frequency hearing loss in BXD recombinant inbred strains.
abstract: The DBA/2J inbred strain of mice has been used extensively in hearing research as it suffers from early-onset, progressive hearing loss. Initially, it mostly affects high frequencies, but already at 2-3 months hearing loss becomes broad. In search for hearing loss genes other than Cadherin 23 (otocadherin) and fascin-2, which make a large contribution to the high-frequency deficits, we used a large set of the genetic reference population of BXD recombinant inbred strains. For frequencies 4, 8, 16 and 32 kHz, auditory brainstem response hearing thresholds were longitudinally determined from 2-3 up to 12 weeks of age. Apart from a significant, broad quantitative trait locus (QTL) for high-frequency hearing loss on chromosome 11 containing the fascin-2 gene, we found a novel, small QTL for low-frequency hearing loss on chromosome 18, from hereon called ahl9. Real-time quantitative polymerase chain reaction of organs of Corti, isolated from a subset of strains, showed that a limited number of genes at the QTL were expressed in the organ of Corti. Of those genes, several showed significant expression differences based on the parental line contributing to the allele. Our results may aid in the future identification of genes involved in low-frequency, early-onset hearing loss.
authors.affiliation: Department of Neuroscience.|Department of Otorhinolaryngology, Erasmus MC, Rotterdam, The Netherlands.
authors.forename: A P
authors.initials: AP
authors.lastname: Nagtegaal
authors.affiliation: Center for Neurogenomics and Cognitive Research, Neuroscience Campus Amsterdam, VU University, Amsterdam, The Netherlands.
authors.forename: S
authors.initials: S
authors.lastname: Spijker
authors.affiliation: Department of Neuroscience.|Department of Otorhinolaryngology, Erasmus MC, Rotterdam, The Netherlands.
authors.forename: T T H
authors.initials: TT
authors.lastname: Crins
authors.affiliation: Department of Neuroscience.
authors.forename: J G G
authors.initials: JG
authors.lastname: Borst
mesh_terms: D000367:Age Factors; D000818:Animals; D001309:Auditory Threshold; D033481:Chromosomes, Mammalian; D016057:Evoked Potentials, Auditory, Brain Stem / Q000235:genetics; D005260:Female; D005786:Gene Expression Regulation / Q000235:genetics; D056726:Genetic Association Studies; D034381:Hearing Loss / Q000235:genetics*; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains / Q000235:genetics*; D040641:Quantitative Trait Loci / Q000235:genetics*; D013045:Species Specificity