Redundancy in tumor necrosis factor (TNF) and lymphotoxin (LT) signaling in vivo: Mice with inactivation of the entire TNF/LT locus versus single-knockout mice Journal Article
| Authors: | Kuprash, D. V.; Alimzhanov, M. B.; Tumanov, A. V.; Grivennikov, S. I.; Shakhov, A. N.; Drutskaya, L. N.; Marino, M. W.; Turetskaya, R. L.; Anderson, A. O.; Rajewsky, K.; Pfeffer, K.; Nedospasov, S. A. |
| Article Title: | Redundancy in tumor necrosis factor (TNF) and lymphotoxin (LT) signaling in vivo: Mice with inactivation of the entire TNF/LT locus versus single-knockout mice |
| Abstract: | Homologous genes and gene products often have redundant physiological functions. Members of the tumor necrosis factor (TNF) family of cytokines can signal activation, proliferation, differentiation, costimulation, inhibition, or cell death, depending on the type and status of the target cell. TNF, lymphotoxin α (LTα), and LTβ form a subfamily of a larger family of TNF-related ligands with their genes being linked within a compact 12-kb cluster inside the major histocompatibility complex locus. Singly TNF-, LTα-, and LTβ-deficient mice share several phenotypic features, suggesting that TNF/LT signaling pathways may regulate overlapping sets of target genes. In order to directly address the issue of redundancy of TNF/LT signaling, we used the Cre-loxP recombination system to create mice with a deletion of the entire TNF/LT locus. Mice with a triple LTβ/TNF/LTα deficiency essentially manifest a combination of LT and TNF single-knockout phenotypes, except for microarchitecture of the spleen, where the disorder of lymphoid cell positioning and functional T- and B-cell compartmentalization is severer than that found in TNF or LT single-knockout mice. Thus, our data support the notion that TNF and LT have largely nonredundant functions in vivo. |
| Keywords: | signal transduction; controlled study; nonhuman; t lymphocyte; t-lymphocytes; animal cell; mouse; phenotype; animals; mice; mice, knockout; animal tissue; gene targeting; cell compartmentalization; gene expression; spleen; animal experiment; animal model; mice, mutant strains; gene locus; gene function; b lymphocyte; animalia; b-lymphocytes; gene expression regulation; genetic recombination; tumor necrosis factor-alpha; antibody response; gene control; gene inactivation; leukocyte count; lymphoid tissue; knockout mouse; tumor necrosis factor; multigene family; lymphoid cell; lymphotoxin; leukocytes; lymphotoxin-alpha; priority journal; article |
| Journal Title: | Molecular and Cellular Biology |
| Volume: | 22 |
| Issue: | 24 |
| ISSN: | 0270-7306 |
| Publisher: | American Society for Microbiology |
| Date Published: | 2002-12-01 |
| Start Page: | 8626 |
| End Page: | 8634 |
| Language: | English |
| DOI: | 10.1128/mcb.22.24.8626-8634.2002 |
| PUBMED: | 12446781 |
| PROVIDER: | scopus |
| PMCID: | PMC139867 |
| DOI/URL: | |
| Notes: | Export Date: 14 November 2014 -- Source: Scopus |
