loading page

Clonality, trafficking, and molecular alterations among Hprt mutant T lymphocytes isolated from control mice versus mice treated with N-ethyl-N-nitrosourea
  • +3
  • Stephen Judice,
  • Hillary Sussman,
  • Dale Walker,
  • J. O'Neill,
  • Richard Albertini,
  • Vernon Walker
Stephen Judice
University of Vermont
Author Profile
Hillary Sussman
Cold Spring Harbor Laboratory Press
Author Profile
Dale Walker
The Burlington HC Research Group, Inc.
Author Profile
J. O'Neill
University of Vermont
Author Profile
Richard Albertini
University of Vermont
Author Profile
Vernon Walker
University of Vermont

Corresponding Author:[email protected]

Author Profile


Mutations in T lymphocytes (T-cells) are informative quantitative markers for environmental mutagen exposures, but risk extrapolations from rodent models to humans also requires understanding how T-cell development and proliferation kinetics impact mutagenic outcomes. Rodent studies have shown that patterns in chemical-induced mutations in the hypoxanthine-guanine phosphoribosyltransferase (Hprt) gene of T-cells differ between lymphoid organs. The current work was performed to obtain knowledge of the relationships between maturation events during T-cell development and changes in chemical-induced mutant frequencies over time in differing immune compartments of a mouse model. A novel RTPCR based method was developed to determine the specific T-cell receptor beta (Tcrb) gene mRNA expressed in mouse T-cell isolates, enabling sequence analysis of the PCR product that then identifies the specific hypervariable CDR3 junctional region of the expressed Tcrb gene for individual isolates. Characterization of spontaneous Hprt mutant isolates from the thymus, spleen, and lymph nodes of control mice for their Tcrb gene expression found evidence of in vivo clonal amplifications of Hprt mutants and their trafficking between tissues in the same animal. Concurrent analyses of Hprt mutations and Tcrb gene rearrangements in different lymphoid tissues of control versus N-ethyl-N-nitrosourea-exposed mice permitted elucidation of the localization and timing of mutational events in T-cells, establishing that mutagenesis occurs primarily in the pre-rearrangement replicative period in pre-thymic/thymic populations. These findings demonstrate that chemical-induced mutagenic burden is determined by the combination of mutagenesis and T-cell clonal expansion, processes with roles in immune function and the pathogenesis of autoimmune disease and cancer.
06 Sep 2023Submitted to Environmental and Molecular Mutagenesis
07 Sep 2023Submission Checks Completed
07 Sep 2023Assigned to Editor
07 Sep 2023Review(s) Completed, Editorial Evaluation Pending
18 Sep 2023Reviewer(s) Assigned
03 Nov 20231st Revision Received
07 Nov 2023Submission Checks Completed
07 Nov 2023Assigned to Editor
07 Nov 2023Review(s) Completed, Editorial Evaluation Pending
10 Nov 2023Editorial Decision: Accept