Quantitative trait loci on chromosome 5 for susceptibility to          frequency-specific effects on hearing in DBA/2J mice

Sari SUZUKI; Masashi ISHIKAWA; Takuya UEDA; Yasuhiro OHSHIBA; Yuki MIYASAKA; Kazuhiro OKUMURA; Michinari YOKOHAMA; Choji TAYA; Kunie MATSUOKA; Yoshiaki KIKKAWA

doi:10.1538/expanim.14-0110

Originals

Quantitative trait loci on chromosome 5 for susceptibility to frequency-specific effects on hearing in DBA/2J mice

Sari SUZUKI, Masashi ISHIKAWA, Takuya UEDA, Yasuhiro OHSHIBA, Yuki MIYASAKA, Kazuhiro OKUMURA, Michinari YOKOHAMA, Choji TAYA, Kunie MATSUOKA, Yoshiaki KIKKAWA

Author information

Sari SUZUKI
Mammalian Genetics Project, Department of Genome Medicine, Tokyo Metropolitan Institute of Medical Science, 2-1-6 Kamikitazawa, Setagaya-ku, Tokyo 156-8506, Japan
Department of Bioproduction, Tokyo University of Agriculture, 196 Yasaka, Abashiri, Hokkaido 099-2493, Japan
Masashi ISHIKAWA
Department of Bioproduction, Tokyo University of Agriculture, 196 Yasaka, Abashiri, Hokkaido 099-2493, Japan
Takuya UEDA
Department of Bioproduction, Tokyo University of Agriculture, 196 Yasaka, Abashiri, Hokkaido 099-2493, Japan
Yasuhiro OHSHIBA
Mammalian Genetics Project, Department of Genome Medicine, Tokyo Metropolitan Institute of Medical Science, 2-1-6 Kamikitazawa, Setagaya-ku, Tokyo 156-8506, Japan
Graduate School of Medical and Dental Sciences, Niigata University, 1–757 Asahimachi, Niigata 951-8510, Japan
Yuki MIYASAKA
Mammalian Genetics Project, Department of Genome Medicine, Tokyo Metropolitan Institute of Medical Science, 2-1-6 Kamikitazawa, Setagaya-ku, Tokyo 156-8506, Japan
Graduate School of Medical and Dental Sciences, Niigata University, 1–757 Asahimachi, Niigata 951-8510, Japan
Kazuhiro OKUMURA
Mammalian Genetics Project, Department of Genome Medicine, Tokyo Metropolitan Institute of Medical Science, 2-1-6 Kamikitazawa, Setagaya-ku, Tokyo 156-8506, Japan
Laboratory of Experimental Animals, Chiba Cancer Center Research Institute, 666-2 Nitona-cho, Chuo-ku, Chiba 260-8717, Japan
Michinari YOKOHAMA
Department of Bioproduction, Tokyo University of Agriculture, 196 Yasaka, Abashiri, Hokkaido 099-2493, Japan
Choji TAYA
Laboratory for Transgenic Technology, Tokyo Metropolitan Institute of Medical Science, 2-1-6 Kamikitazawa, Setagaya-ku, Tokyo 156-8506, Japan
Kunie MATSUOKA
Mammalian Genetics Project, Department of Genome Medicine, Tokyo Metropolitan Institute of Medical Science, 2-1-6 Kamikitazawa, Setagaya-ku, Tokyo 156-8506, Japan
Yoshiaki KIKKAWA
Mammalian Genetics Project, Department of Genome Medicine, Tokyo Metropolitan Institute of Medical Science, 2-1-6 Kamikitazawa, Setagaya-ku, Tokyo 156-8506, Japan
Graduate School of Medical and Dental Sciences, Niigata University, 1–757 Asahimachi, Niigata 951-8510, Japan

Keywords: ahllocus, chromosome 5, DBA/2J, early-onset hearing loss, quantitative trait loci (QTL)

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Supplementary material

2015 Volume 64 Issue 3 Pages 241-251

DOI https://doi.org/10.1538/expanim.14-0110

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Abstract

The DBA/2J strain is a model for early-onset, progressive hearing loss in humans, as confirmed in the present study. DBA/2J mice showed progression of hearing loss to low-frequency sounds from ultrasonic-frequency sounds and profound hearing loss at all frequencies before 7 months of age. It is known that the early-onset hearing loss of DBA/2J mice is caused by affects in the ahl (Cdh23^ahl) and ahl8 (Fscn2^ahl8) alleles of the cadherin 23 and fascin 2 genes, respectively. Although the strong contributions of the Fscn2^ahl8 allele were detected in hearing loss at 8- and 16-kHz stimuli with LOD scores of 5.02 at 8 kHz and 8.84 at 16 kHz, hearing loss effects were also demonstrated for three new quantitative trait loci (QTLs) for the intervals of 50.3–54.5, 64.6–119.9, and 119.9–137.0 Mb, respectively, on chromosome 5, with significant LOD scores of 2.80–3.91 for specific high-frequency hearing loss at 16 kHz by quantitative trait loci linkage mapping using a (DBA/2J × C57BL/6J) F₁ × DBA/2J backcross mice. Moreover, we showed that the contribution of Fscn2^ahl8 to early-onset hearing loss with 32-kHz stimuli is extremely low and raised the possibility of effects from the Cdh23^ahl allele and another dominant quantitative trait locus (loci) for hearing loss at this ultrasonic frequency. Therefore, our results suggested that frequency-specific QTLs control early-onset hearing loss in DBA/2J mice.

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