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A Novel Gene Essential for the Development of Single Positive Thymocytes.
- Source :
- Molecular & Cellular Biology; Sep2009, Vol. 29 Issue 18, p5128-5135, 8p
- Publication Year :
- 2009
-
Abstract
- A critical step during intrathymic T-cell development is the transition of CD4<superscript>+</superscript> CD8<superscript>+</superscript> double-positive (DP) cells to the major histocompatibility complex class I (MHC-I)-restricted CD4<superscript>-</superscript> CD8<superscript>+</superscript> and MHC-II-restricted CD4<superscript>+</superscript> CD8<superscript>-</superscript> 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. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 02707306
- Volume :
- 29
- Issue :
- 18
- Database :
- Complementary Index
- Journal :
- Molecular & Cellular Biology
- Publication Type :
- Academic Journal
- Accession number :
- 44184639
- Full Text :
- https://doi.org/10.1128/MCB.00793-09