A QTL on Chr 5 modifies hearing loss associated with the fascin-2 variant of DBA/2J mice

A QTL on Chr 5 modifies hearing loss associated with the fascin-2 variant of DBA/2J mice Inbred mouse strains serve as important models for human presbycusis or age-related hearing loss. We previously mapped a locus (ahl8) contributing to the progressive hearing loss of DBA/2J (D2) mice and later showed that a missense variant of the Fscn2 gene, unique to the D2 inbred strain, was responsible for the ahl8 effect. Although ahl8 can explain much of the hearing loss difference between C57BL/6J (B6) and D2 strain mice, other loci also contribute. Here, we present results of our linkage analyses to map quantitative trait loci (QTLs) that modify the severity of hearing loss associated with the D2 strain Fscn2 ahl8 allele. We searched for modifier loci by analyzing 31 BXD recombinant inbred (RI) lines fixed for the predisposing D2-derived Fscn2 ahl8/ahl8 genotype and found a statistically significant linkage association of threshold means with a QTL on Chr 5, which we designated M5ahl8. The highest association (LOD 4.6) was with markers at the 84–90 Mb position of Chr 5, which could explain about 46 % of the among-RI strain variation in auditory brainstem response (ABR) threshold means. The semidominant nature of the modifying effect of M5ahl8 on the Fscn2 ahl8/ahl8 phenotype was demonstrated by analysis of a backcross involving D2 and B6.D2-Chr11D/LusJ strain mice. The Chr 5 map position of M5ahl8 and the D2 origin of its susceptibility allele correspond to Tmc1m4, a previously reported QTL that modifies outer hair cell degeneration in Tmc1 Bth mutant mice, suggesting that M5ahl8 and Tmc1m4 may represent the same gene affecting maintenance of stereocilia structure and function during aging. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Mammalian Genome Springer Journals

A QTL on Chr 5 modifies hearing loss associated with the fascin-2 variant of DBA/2J mice

Loading next page...
 
/lp/springer_journal/a-qtl-on-chr-5-modifies-hearing-loss-associated-with-the-fascin-2-3NY0q9vLC8
Publisher
Springer US
Copyright
Copyright © 2015 by Springer Science+Business Media New York
Subject
Life Sciences; Cell Biology; Anatomy; Zoology
ISSN
0938-8990
eISSN
1432-1777
D.O.I.
10.1007/s00335-015-9574-y
Publisher site
See Article on Publisher Site

Abstract

Inbred mouse strains serve as important models for human presbycusis or age-related hearing loss. We previously mapped a locus (ahl8) contributing to the progressive hearing loss of DBA/2J (D2) mice and later showed that a missense variant of the Fscn2 gene, unique to the D2 inbred strain, was responsible for the ahl8 effect. Although ahl8 can explain much of the hearing loss difference between C57BL/6J (B6) and D2 strain mice, other loci also contribute. Here, we present results of our linkage analyses to map quantitative trait loci (QTLs) that modify the severity of hearing loss associated with the D2 strain Fscn2 ahl8 allele. We searched for modifier loci by analyzing 31 BXD recombinant inbred (RI) lines fixed for the predisposing D2-derived Fscn2 ahl8/ahl8 genotype and found a statistically significant linkage association of threshold means with a QTL on Chr 5, which we designated M5ahl8. The highest association (LOD 4.6) was with markers at the 84–90 Mb position of Chr 5, which could explain about 46 % of the among-RI strain variation in auditory brainstem response (ABR) threshold means. The semidominant nature of the modifying effect of M5ahl8 on the Fscn2 ahl8/ahl8 phenotype was demonstrated by analysis of a backcross involving D2 and B6.D2-Chr11D/LusJ strain mice. The Chr 5 map position of M5ahl8 and the D2 origin of its susceptibility allele correspond to Tmc1m4, a previously reported QTL that modifies outer hair cell degeneration in Tmc1 Bth mutant mice, suggesting that M5ahl8 and Tmc1m4 may represent the same gene affecting maintenance of stereocilia structure and function during aging.

Journal

Mammalian GenomeSpringer Journals

Published: Jun 20, 2015

References

You’re reading a free preview. Subscribe to read the entire article.


DeepDyve is your
personal research library

It’s your single place to instantly
discover and read the research
that matters to you.

Enjoy affordable access to
over 18 million articles from more than
15,000 peer-reviewed journals.

All for just $49/month

Explore the DeepDyve Library

Search

Query the DeepDyve database, plus search all of PubMed and Google Scholar seamlessly

Organize

Save any article or search result from DeepDyve, PubMed, and Google Scholar... all in one place.

Access

Get unlimited, online access to over 18 million full-text articles from more than 15,000 scientific journals.

Your journals are on DeepDyve

Read from thousands of the leading scholarly journals from SpringerNature, Elsevier, Wiley-Blackwell, Oxford University Press and more.

All the latest content is available, no embargo periods.

See the journals in your area

DeepDyve

Freelancer

DeepDyve

Pro

Price

FREE

$49/month
$360/year

Save searches from
Google Scholar,
PubMed

Create lists to
organize your research

Export lists, citations

Read DeepDyve articles

Abstract access only

Unlimited access to over
18 million full-text articles

Print

20 pages / month

PDF Discount

20% off