A novel QTL underlying early‐onset, low‐frequency hearing loss in BXD recombinant inbred strains

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 (otoca...

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Bibliographic Details
Published in:Genes, brain and behavior brain and behavior, 2012-11, Vol.11 (8), p.911-920
Main Authors: Nagtegaal, A. P., Spijker, S., Crins, T. T. H., Borst, J. G. G.
Format: Article
Language:English
Subjects:
Age Factors
Age‐related hearing loss
Animals
auditory brainstem response
Auditory Threshold
BXD recombinant inbred strains
Chromosomes, Mammalian
complex trait analysis
Ears & hearing
Evoked Potentials, Auditory, Brain Stem - genetics
Female
Gene Expression Regulation - genetics
Genes
Genetic Association Studies
Hearing loss
Hearing Loss - genetics
Hearing protection
heritability
Male
Mice
Mice, Inbred Strains - genetics
qPCR
QTL
Quantitative Trait Loci - genetics
Species Specificity
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Summary: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. A novel QTL on chromosome 18, ahl9, underlying early‐onset, low‐frequency hearing loss in BXD recombinant inbred strains.
ISSN:1601-1848
1601-183X
DOI:10.1111/j.1601-183X.2012.00845.x