A novel gene essential for the development of single positive thymocytes

Kiyokazu Kakugawa, Takuwa Yasuda, Ikuo Miura, Ayako Kobayashi, Hitomi Fukiage, Rumi Satoh, Masashi Matsuda, Haruhiko Koseki, Shigeharu Wakana, Hiroshi Kawamoto, Hisahiro Yoshida

Research output: Contribution to journalArticlepeer-review

43 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)5128-5135
Number of pages8
JournalMolecular and Cellular Biology
Volume29
Issue number18
DOIs
Publication statusPublished - 09-2009
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Molecular Biology
  • Cell Biology

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