A mutation of Ikbkg causes immune deficiency without impairing degradation of IkappaB alpha
| Autor: | Elaine Pirie, Bruce Beutler, David Nemazee, Philippe Krebs, Christoph Huber, Nora G. Smart, Kevin Khovananth, Gunilla B. Karlsson Hedestam, Yu Xia, Michael Berger, Celine Eidenschenk, Gerald M. McInerney, Owen M. Siggs, Carrie N. Arnold |
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| Jazyk: | angličtina |
| Rok vydání: | 2016 |
| Předmět: |
Male
Ectodermal dysplasia Blotting Western Mice Transgenic Biology medicine.disease_cause Nitric Oxide T-Lymphocytes Regulatory 03 medical and health sciences Mice 0302 clinical medicine Immune system IKBKG medicine Animals Loss function 030304 developmental biology 0303 health sciences Toll-like receptor Mutation Multidisciplinary Toll-Like Receptors Immunologic Deficiency Syndromes Intracellular Signaling Peptides and Proteins Biological Sciences medicine.disease Flow Cytometry Null allele I-kappa B Kinase IκBα Mutagenesis Ethylnitrosourea Cancer research Cytokines Lymph Nodes 030215 immunology Signal Transduction |
| Zdroj: | Proceedings of the National Academy of Sciences of the United States of America |
| Popis: | Null alleles of the gene encoding NEMO (NF-κB essential modulator) are lethal in hemizygous mice and men, whereas hypomorphic alleles typically cause a syndrome of immune deficiency and ectodermal dysplasia. Here we describe an allele of Ikbkg in mice that impaired Toll-like receptor signaling, lymph node formation, development of memory and regulatory T cells, and Ig production, but did not cause ectodermal dysplasia. Degradation of IκBα, which is considered a primary requirement for NEMO-mediated immune signaling, occurred normally in response to Toll-like receptor stimulation, yet ERK phosphorylation and NF-κB p65 nuclear translocation were severely impaired. This selective loss of function highlights the immunological importance of NEMO-regulated pathways beyond IκBα degradation, and offers a biochemical explanation for rare immune deficiencies in man. |
| Databáze: | OpenAIRE |
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