Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
6808422 | Neurobiology of Aging | 2012 | 10 Pages |
Abstract
We previously mapped a locus (ahl4) on distal Chromosome 10 that contributes to the age-related hearing loss of A/J strain mice. Here, we report on a refined genetic map position for ahl4 and its association with a mutation in the citrate synthase gene (Cs). We mapped ahl4 to the distal-most 7 megabases (Mb) of chromosome 10 by analysis of a new linkage backcross and then further narrowed the interval to 5.5 Mb by analysis of 8 C57BL/6J congenic lines with different A/J-derived segments of chromosome 10. A nucleotide variant in exon 3 of Cs is the only known DNA difference within the ahl4 candidate gene interval that is unique to the A/J strain and that causes a nonsynonymous codon change. Multiple lines of evidence implicate this missense mutation (H55N) as the underlying cause of ahl4-related hearing loss, likely through its effects on mitochondrial adenosine trisphosphate (ATP) and free radical production in cochlear hair cells. The A/J mouse thus provides a new model system for in vivo studies of mitochondrial function and hearing loss.
Keywords
Related Topics
Life Sciences
Biochemistry, Genetics and Molecular Biology
Ageing
Authors
Kenneth R. Johnson, Leona H. Gagnon, Chantal Longo-Guess, Kelly L. Kane,