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.
Kakugawa
Kiyokazu
K
Laboratory for Lymphocyte Development, RIKEN Research Center for Allergy and Immunology, RIKEN Yokohama Institute, Yokohama, Kanagawa, Japan.
Yasuda
Takuwa
T
Miura
Ikuo
I
Kobayashi
Ayako
A
Fukiage
Hitomi
H
Satoh
Rumi
R
Matsuda
Masashi
M
Koseki
Haruhiko
H
Wakana
Shigeharu
S
Kawamoto
Hiroshi
H
Yoshida
Hisahiro
H
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D002874:Chromosome Mapping; D005038:Ethylnitrosourea; D020043:Genes, Essential; D016678:Genome / Q000235:genetics; D051379:Mice; D008817:Mice, Mutant Strains; D008969:Molecular Sequence Data; D020125:Mutation, Missense / Q000235:genetics; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D011506:Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D017386:Sequence Homology, Amino Acid; D017154:Stromal Cells / Q000166:cytology / Q000378:metabolism; D013601:T-Lymphocytes / Q000166:cytology* / Q000378:metabolism*
D011506:Proteins; D005038:Ethylnitrosourea