The absence of Tssc6, a member of the tetraspanin superfamily, does not affect lymphoid development but enhances in vitro T-cell proliferative responses

Tarrant, JA; Groom, J; Metcalf, D; Li, RL; Borobokas, B; Wright, MD; Tarlinton, D; Robb, L

Author(s): Tarrant, JA; Groom, J; Metcalf, D; Li, RL; Borobokas, B; Wright, MD; Tarlinton, D; Robb, L;
Details: Publication Year 2002-07,Volume 22,Issue #14,Page 5006-5018
Journal Title: MOLECULAR AND CELLULAR BIOLOGY
Publication Type: Journal Article
Abstract: The tetraspanins are a family of integral membrane proteins with four transmembrane domains. These molecules form multimolecular networks on the surfaces of many different cell types. Gene-targeting studies have revealed a role for tetraspanins in B- and T-lymphocyte function. We have isolated and deleted a novel tetraspanin, Tssc6, which is expressed exclusively in hematopoietic and lymphoid organs. Using a gene-trapping strategy, we generated an embryonic stem (ES) cell line with an insertion in the Tssc6 locus. Mice were derived from these ES cells and, using RNase protection and reverse transcription-PCR, we demonstrated that the insertion resulted in a null mutation of the Tssc6 allele. Mice homozygous for the gene trap insertion (Tssc6(gt/gt) mice) were viable and fertile, with normal steady-state hematopoiesis. Furthermore, responses to hemolysis and granulocyte colony-stimulating factor-induced granulopoiesis were equivalent to those of wildtype mice. Lymphoid development was normal in Tssc6(gt/gt) mice. Whereas Tssc6(gt/gt) B cells responded normally to lipopolysaccharide, anti-CD40, and anti-immunoglobulin M stimulation, Tssc6(gt/gt) T cells showed enhanced responses to concanavalin A, anti-CD3, and anti-CD28. This increased proliferation by Tssc6-deleted T lymphocytes was due to increased interleukin 2 production following T-cell receptor stimulation. These results demonstrate that Tssc6 is not required for normal development of the hematopoietic system but may play a role in the negative regulation of peripheral T-lymphocyte proliferation.
Publisher: AMER SOC MICROBIOLOGY
Keywords: COLONY-STIMULATING FACTOR; TRANSMEMBRANE-4 SUPERFAMILY; SIGNAL-TRANSDUCTION; B-LYMPHOCYTES; MOUSE EMBRYOS; MICE LACKING; CD81; GENE; CD9; RECEPTOR
Publisher's Version: https://doi.org/10.1128/MCB.22.14.5006-5018.2002
Terms of Use/Rights Notice: Refer to copyright notice on published article.

Creation Date: 2002-07-01 12:00:00