Rac1 deletion causes thymic atrophy

PLoS One. 2011 Apr 29;6(4):e19292. doi: 10.1371/journal.pone.0019292.


The thymic stroma supports T lymphocyte development and consists of an epithelium maintained by thymic epithelial progenitors. The molecular pathways that govern epithelial homeostasis are poorly understood. Here we demonstrate that deletion of Rac1 in Keratin 5/Keratin 14 expressing embryonic and adult thymic epithelial cells leads to loss of the thymic epithelial compartment. Rac1 deletion led to an increase in c-Myc expression and a generalized increase in apoptosis associated with a decrease in thymic epithelial proliferation. Our results suggest Rac1 maintains the epithelial population, and equilibrium between Rac1 and c-Myc may control proliferation, apoptosis and maturation of the thymic epithelial compartment. Understanding thymic epithelial maintenance is a step toward the dual goals of in vitro thymic epithelial cell culture and T cell differentiation, and the clinical repair of thymic damage from graft-versus-host-disease, chemotherapy or irradiation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Atrophy
  • Cell Proliferation
  • Crosses, Genetic
  • Flow Cytometry
  • Gene Deletion
  • Gene Expression Regulation
  • Green Fluorescent Proteins / metabolism
  • Heterozygote
  • Homeostasis
  • Kidney / embryology
  • Mice
  • Microscopy, Fluorescence / methods
  • Neuropeptides / genetics
  • Neuropeptides / physiology*
  • Promoter Regions, Genetic
  • Thymus Gland / embryology
  • Thymus Gland / pathology*
  • Time Factors
  • rac GTP-Binding Proteins / genetics
  • rac GTP-Binding Proteins / physiology*
  • rac1 GTP-Binding Protein


  • Neuropeptides
  • Rac1 protein, mouse
  • Green Fluorescent Proteins
  • rac GTP-Binding Proteins
  • rac1 GTP-Binding Protein