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Molecular and Cellular Biology, July 2002, p. 5006-5018, Vol. 22, No. 14
0270-7306/02/$04.00+0     DOI: 10.1128/MCB.22.14.5006-5018.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.

The Absence of Tssc6, a Member of the Tetraspanin Superfamily, Does Not Affect Lymphoid Development but Enhances In Vitro T-Cell Proliferative Responses

Jacqueline M. Tarrant,^1* Joanna Groom,^1, Donald Metcalf,¹ Ruili Li,¹ Bette Borobokas,¹ Mark D. Wright,² David Tarlinton,¹ and Lorraine Robb¹

The Walter and Eliza Hall Institute of Medical Research, Royal Melbourne Hospital, 3050 Victoria,¹ Austin Research Institute, Austin & Repatriation Medical Centre, Heidelberg, 3084 Victoria, Australia²

Received 21 December 2001/ Returned for modification 12 February 2002/ Accepted 17 April 2002

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 wild-type 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.

Present address: Department of Arthritis and Inflammation, The Garvan Institute of Medical Research, Darlinghurst, New South Wales 2010, Australia.

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