Differential gene expression in CD3e- and RAG1-deficient thymuses: definition of a set of genes potentially involved in thymocyte maturation

Abstract

A set of 3000 mouse thymus cDNAs was analyzed by extensive measurement of expression using complex-probe hybridization of DNA arrays ("quantitative differential screening"). The complex probes were initially prepared using total thymus RNA isolated from C57BL/6 wild-type (WT), CD3epsilon- and RAG1-deficient mice. Over 100 clones displaying over- or under-expression by at least a factor of two between WT and knockout (KO) thymuses were further analyzed by measuring hybridization signatures with probes from a wide range of KO thymuses, cell types, organs, and embryonic thymuses. A restricted set of clones was selected by virtue of their expression spectra (modulation in KO thymuses and thymocytes, lymphoid cell specificity, and differential expression during embryonic thymus development), sequenced at one extremity, and compared to sequences in databases. Clones corresponding to previously identified genes (e.g., Tcrbeta, Tcf1 or CD25) showed expression patterns that were consistent with existing data. Ten distinct clones corresponding to new genes were subjected to further study: Northern blot hybridization, in situ hybridization on thymus sections, and partial or complete mRNA sequence determination. Among these genes, we report a new serine peptidase highly expressed in cortical epithelial cells that we have named thymus-specific serine peptidase (TSSP), and an acidic protein expressed in thymocytes and of unknown function that we have named thymus-expressed acidic protein (TEAP). This approach identifies new molecules likely to be involved in thymocyte differentiation and function.

Identification of candidate tumor suppressor genes inactivated by promoter methylation in melanoma

“…The TP53INP1 gene (tumor protein 53-induced nuclear protein 1), cloned by three different teams (Carrier et al, 1999;Okamura et al, 2001;Tomasini et al, 2001), encodes a p53-inducible protein which promotes apoptosis and cell cycle arrest in G1 phase (Tomasini et al, 2003). Decreased TP53INP1 expression has been described in breast carcinoma (Ito et al, 2006b), anaplastic carcinoma of the thyroid (Ito et al, 2006a) and gastric cancer, where its loss was inversely correlated with tumor size, positive lymph node metastasis and aberrant p53 expression (Jiang et al, 2006).…”

Alternatively spliced transcripts of the thymus-specific protease PRSS16 are differentially expressed in human thymus

“…Then, the 'infant' expression pattern of the PRSS16 splice variants observed in young individuals and in adult MG patients with thymoma might contribute to the previously observed increase in recent thymic emigrant cells in patients with MG-associated thymoma. 30,31 Interestingly, Prss16 in mice is expressed in the cortical thymic epithelium 32 and reaches its highest level in 16-day-old embryos. 3 Furthermore, while in WT mice Prss16 is weakly expressed, in T-cell deficient mice such as CD3e-and RAG1-knockout mice, the expression of this protease is dramatically increased.…”

“…3 Furthermore, while in WT mice Prss16 is weakly expressed, in T-cell deficient mice such as CD3e-and RAG1-knockout mice, the expression of this protease is dramatically increased. 32 Thus, PRSS16 may contribute to the development of the embryogenic thymus and to regulatory mechanisms during thymopoiesis. Nearly two-thirds of early-onset patients with TFH are HLA-B8 and DR3 positive, while B7 and DR2 are frequent alleles found in patients developing myasthenia symptoms at later ages (reviewed in Vincent et al 24 ).…”

Spatial (Tbata) expression in mature medullary thymic epithelial cells

“…Using DNA chip technology we isolated the Spatial gene (Stromal Protein Associated with Thymii and Lymph node), also known as Tbata (thymus, brain and testes associated), by an approach based on differential screening between different knock-out mice models exhibiting distinct thymic immunodeficiencies [7]. This analysis led to the identification of three adult variants of the Spatial gene expressed in the thymus [8].…”

“…TEC are required both for thymus organogenesis and for the promotion of most if not all stages of thymocyte maturation [3,4]. Understanding the molecular mechanisms regulating TEC differentiation and function provides crucial insights into mechanisms controlling T-cell development in the thymus.Using DNA chip technology we isolated the Spatial gene (Stromal Protein Associated with Thymii and Lymph node), also known as Tbata (thymus, brain and testes associated), by an approach based on differential screening between different knock-out mice models exhibiting distinct thymic immunodeficiencies [7]. This analysis led to the identification of three adult variants of the Spatial gene expressed in the thymus [8].…”