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Phenotypic characterization of an allelic variant of the mechanistic target of rapamycin (Mtor)

Friday, November 08, 2013 — Poster Session III

10:00 a.m. – 12:00 p.m.

FAES Academic Center (Upper-Level Terrace)




  • J. M. Gary
  • W. DuBois
  • S. Zhang
  • K. Zhang
  • J. K. Simmons
  • D. Tran
  • S. Lynch
  • A. Michalowski
  • B. Mock


The PI3K/AKT/MTOR pathway is frequently dysregulated in cancer. We discovered an allelic variant of Mtor (C1977T) in BALB/cAnPt mice, which results in a single amino acid substitution (R628C) that is predicted to be damaging. To study this allelic variant, we developed a knock-in (KI) that carries this allele of Mtor on a B6;129 background. We also compared the mRNA expression in bone marrow and B220+ splenocytes (B cells) between WT and KI mice with or without pristane treatment. Network enrichment analysis revealed that top networks included DNA replication and repair and that multiple genes involved in DNA damage repair (DDR) were down regulated in the bone marrow of pristane-treated mice. To assess differential DDR, WT and KI mouse embryonic fibroblasts (MEFs) were immortalized with SV40 Large T antigen and are being subjected to treatment with several DNA damaging agents.

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