Exome sequencing of senescence-accelerated mice (SAM) reveals deleterious mutations in degenerative disease-causing genes

Kumpei Tanisawa, Eri Mikami, Noriyuki Fuku, Yoko Honda, Shuji Honda, Ikuro Ohsawa, Masafumi Ito, Shogo Endo, Kunio Ihara, Kinji Ohno, Yuki Kishimoto, Akihito Ishigami, Naoki Maruyama, Motoji Sawabe, Hiroyoshi Iseki, Yasushi Okazaki, Sanae Hasegawa-Ishii, Shiro Takei, Atsuyoshi Shimada, Masanori HosokawaMasayuki Mori, Keiichi Higuchi, Toshio Takeda, Mitsuru Higuchi, Masashi Tanaka

研究成果: Article査読

22 被引用数 (Scopus)

抄録

Background: Senescence-accelerated mice (SAM) are a series of mouse strains originally derived from unexpected crosses between AKR/J and unknown mice, from which phenotypically distinct senescence-prone (SAMP) and -resistant (SAMR) inbred strains were subsequently established. Although SAMP strains have been widely used for aging research focusing on their short life spans and various age-related phenotypes, such as immune dysfunction, osteoporosis, and brain atrophy, the responsible gene mutations have not yet been fully elucidated.Results: To identify mutations specific to SAMP strains, we performed whole exome sequencing of 6 SAMP and 3 SAMR strains. This analysis revealed 32,019 to 38,925 single-nucleotide variants in the coding region of each SAM strain. We detected Ogg1 p.R304W and Mbd4 p.D129N deleterious mutations in all 6 of the SAMP strains but not in the SAMR or AKR/J strains. Moreover, we extracted 31 SAMP-specific novel deleterious mutations. In all SAMP strains except SAMP8, we detected a p.R473W missense mutation in the Ldb3 gene, which has been associated with myofibrillar myopathy. In 3 SAMP strains (SAMP3, SAMP10, and SAMP11), we identified a p.R167C missense mutation in the Prx gene, in which mutations causing hereditary motor and sensory neuropathy (Dejerine-Sottas syndrome) have been identified. In SAMP6 we detected a p.S540fs frame-shift mutation in the Il4ra gene, a mutation potentially causative of ulcerative colitis and osteoporosis.Conclusions: Our data indicate that different combinations of mutations in disease-causing genes may be responsible for the various phenotypes of SAMP strains.

本文言語English
論文番号248
ジャーナルBMC Genomics
14
1
DOI
出版ステータスPublished - 2013 4 15

ASJC Scopus subject areas

  • Biotechnology
  • Genetics

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