Age-related change in thymic T-cell development is associated with genetic loci on mouse chromosomes 1, 3, and 11

Hui Chen Hsu, John D. Mountz, Robert W. Williams, Brent J. Shelton, Ping Ar Yang, Yasunori Matsuki, Xin Xu, Christopher H. Dodd, Lina Li, Hartmut Geiger, Huang Ge Zhang, Gary Van Zant

Research output: Contribution to journalArticlepeer-review

19 Scopus citations

Abstract

Age-related decline in thymic T-cell development in 22-month-old C57BL/6J X DBA/2J (BXD) recombinant inbred strains of mice was functionally and phenotypically analyzed and genetically mapped. There was a positive correlation of the concanavalin A (Con A)-induced thymocyte proliferative response with the capability of thymocytes to mature to the CD4+CD8+ stage. The accumulation of CD4-CD8- stage of thymocytes in 22-month-old BXD mice was further identified to be associated with a developmental block between the CD25-CD44+ and the CD25+CD44+ stages. The quantitative trait loci regulating the Con A-induced thymocyte proliferative response were mapped to mouse chromosome 1, 3, and 11, nearest to 32.1 centimorgan (cM), 5.6 cM, and 18.0 cM, respectively. Our results suggest that several genetic loci regulate the intra-thymic T-cell maturation process and play an important role in determining age-related decline in thymic T-cell development.

Original languageEnglish
Pages (from-to)1145-1158
Number of pages14
JournalMechanisms of Ageing and Development
Volume123
Issue number8
DOIs
StatePublished - Apr 30 2002

Bibliographical note

Funding Information:
We thank Dr. T. Rogers and Mr. M. Spell of the FACS Core Facility at UAB for operating the FACS. We also thank Dr. F. Hunter and Ms. D. Downs for critical review of the manuscript and Ms. Linda Flurry for excellent secretary work. This work is supported by NIH grants R01 AG 16653, N01 AR 6-2224, and CA 20408, and a Birmingham VAMC Merit Review Grant. Hui-Chen Hsu is a recipient of a grant from the Center for Aging at the University of Alabama at Birmingham. Huang-Ge Zhang is a recipient of Arthritis Foundation Investigator Award. Hartmut Geiger was supported by a fellowship of the Deutsch e Akademie der Naturforscher Leopoldina funded by the Bundesministerium für Bildung und Forschung.

Keywords

  • Aging
  • Quantitative trait loci
  • Recombinant inbred mice
  • T cells
  • Thymic involution

ASJC Scopus subject areas

  • Aging
  • Developmental Biology

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