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

• Tanisawa, Kumpei

• Mikami, Eri

• Fuku, Noriyuki

• Honda, Yoko

• Honda, Shuji

• Ohsawa, Ikuro

• Ito, Masafumi

• Endo, Shogo

• Ihara, Kunio

• Ohno, Kinji

• Kishimoto, Yuki

• Ishigami, Akihito

• Maruyama, Naoki

• Sawabe, Motoji

• Iseki, Hiroyoshi

• Okazaki, Yasushi

• Hasegawa-Ishii, Sanae

• Takei, Shiro

• Shimada, Atsuyoshi

• Hosokawa, Masanori

• Mori, Masayuki

• Higuchi, Keiichi

• Takeda, Toshio

• Higuchi, Mitsuru

• Tanaka, Masashi

Abstract

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.

Article

BMC GENOMICS. 14:248 (2013)

Journal

• BMC GENOMICS

  BMC GENOMICS 14 248-, 2013-04-16

  BIOMED CENTRAL LTD

Keywords

• Exome sequencing
• Senescence-accelerated mice
• Aging

Details

• CRID: 1050001338927112448
• NII Article ID: 120007100717
• NII Book ID: AA12034967
• DOI: 10.1186/1471-2164-14-248
• HANDLE: 10091/00019827
• ISSN: 14712164
• Web Site: https://soar-ir.repo.nii.ac.jp/records/19065
• Web Site: https://link.springer.com/content/pdf/10.1186/1471-2164-14-248.pdf
• Text Lang: en
• Article Type: journal article
• Data Source:
  • IRDB
  • Crossref
  • CiNii Articles
  • KAKEN