These authors contributed equally to this work.
1601-183X/asset/GBB_left.gif?v=1&s=b2b7202fa0960387bd2288aa7028a24d34948ae3)
1601-183X/asset/GBB_right.gif?v=1&s=9e6cb0f477617502403ed682592546c149f07c21)
Original Article
You have free access to this content
A novel QTL underlying early-onset, low-frequency hearing loss in BXD recombinant inbred strains
Article first published online: 8 OCT 2012
DOI: 10.1111/j.1601-183X.2012.00845.x
© 2012 The Authors. Genes, Brain and Behavior © 2012 Blackwell Publishing Ltd and International Behavioural and Neural Genetics Society
Additional Information
How to Cite
Nagtegaal, A. P., Spijker, S., Crins, T. T. H., Neuro-Bsik Mouse Phenomics Consortium and Borst, J. G. G. (2012), A novel QTL underlying early-onset, low-frequency hearing loss in BXD recombinant inbred strains. Genes, Brain and Behavior, 11: 911–920. doi: 10.1111/j.1601-183X.2012.00845.x
Publication History
- Issue published online: 8 NOV 2012
- Article first published online: 8 OCT 2012
- Accepted manuscript online: 18 SEP 2012 12:00AM EST
- Manuscript Accepted: 27 AUG 2012
- Manuscript Revised: 20 AUG 2012
- Manuscript Revised: 23 JUL 2012
- Manuscript Received: 20 JUN 2012
Funded by
- SenterNovem, The Netherlands (Neuro-Bsik Grant). Grant Number: BSIK 03053
- Heinsius Houbolt Fund
Keywords:
- Age-related hearing loss;
- auditory brainstem response;
- BXD recombinant inbred strains;
- complex trait analysis;
- heritability;
- qPCR;
- QTL
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.
