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 RIS Download
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