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A novel gene essential for the development of single positive thymocytes.

A critical step during intrathymic T-cell development is the transition of CD4(+) CD8(+) double-positive (DP) cells to the major histocompatibility complex class I (MHC-I)-restricted CD4(-) CD8(+) and MHC-II-restricted CD4(+) CD8(-) single-positive (SP) cell stage. Here, we identify a novel gene that is essential for this process. Through the T-cell phenotype-based screening of N-ethyl-N-nitrosourea (ENU)-induced mutant mice, we established a mouse line in which numbers of CD4 and CD8 SP thymocytes as well as peripheral CD4 and CD8 T cells were dramatically reduced. Using linkage analysis and DNA sequencing, we identified a missense point mutation in a gene, E430004N04Rik (also known as themis), that does not belong to any known gene family. This orphan gene is expressed specifically in DP and SP thymocytes and peripheral T cells, whereas in mutant thymocytes the levels of protein encoded by this gene were drastically reduced. We generated E430004N04Rik-deficient mice, and their phenotype was virtually identical to that of the ENU mutant mice, thereby confirming that this gene is essential for the development of SP thymocytes.

Pubmed ID: 19620281


  • Kakugawa K
  • Yasuda T
  • Miura I
  • Kobayashi A
  • Fukiage H
  • Satoh R
  • Matsuda M
  • Koseki H
  • Wakana S
  • Kawamoto H
  • Yoshida H


Molecular and cellular biology

Publication Data

September 27, 2009

Associated Grants


Mesh Terms

  • Amino Acid Sequence
  • Animals
  • Base Sequence
  • Chromosome Mapping
  • Ethylnitrosourea
  • Genes, Essential
  • Genome
  • Mice
  • Mice, Mutant Strains
  • Molecular Sequence Data
  • Mutation, Missense
  • Phenotype
  • Polymorphism, Single Nucleotide
  • Proteins
  • Sequence Homology, Amino Acid
  • Stromal Cells
  • T-Lymphocytes