A locus on distal chromosome 11 (ahl8) and its interaction with Cdh23 ahl underlie the early onset, age-related hearing loss of DBA/2J mice.
The DBA/2J inbred strain of mice is used extensively in hearing research, yet little is known about the genetic basis for its early onset, progressive hearing loss. To map underlying genetic factors we analyzed recombinant inbred strains and linkage backcrosses. Analysis of 213 mice from 31 BXD recombinant inbred strains detected linkage of auditory brain-stem response thresholds with a locus on distal chromosome 11, which we designate ahl8. Analysis of 225 N2 mice from a backcross of (C57BL/6JxDBA/2J) F1 hybrids to DBA/2J mice confirmed this linkage (LOD>50) and refined the ahl8 candidate gene interval. Analysis of 214 mice from a backcross of (B6.CAST-Cdh23 Ahl+ xDBA/2J) F1 hybrids to DBA/2J mice demonstrated a genetic interaction of Cdh23 with ahl8. We conclude that ahl8 is a major contributor to the hearing loss of DBA/2J mice and that its effects are dependent on the predisposing Cdh23 ahl genotype of this strain.
Johnson
Kenneth R
KR
The Jackson Laboratory, Bar Harbor, ME 04609, USA. ken.johnson@jax.org
Longo-Guess
Chantal
C
Gagnon
Leona H
LH
Yu
Heping
H
Zheng
Qing Yin
QY
D000375:Aging / Q000235:genetics*; D000818:Animals; D015820:Cadherins / Q000235:genetics*; D033481:Chromosomes, Mammalian / Q000235:genetics*; D003433:Crosses, Genetic; D020022:Genetic Predisposition to Disease; D005838:Genotype; D034381:Hearing Loss / Q000235:genetics*; D051379:Mice; D040641:Quantitative Trait Loci / Q000235:genetics*
D015820:Cadherins; C499091:Cdh23 protein, mouse