Null alleles of the gene encodingNEMO(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 ofmemory 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.
|Original language||American English|
|Number of pages||6|
|Journal||Proceedings of the National Academy of Sciences of the United States of America|
|State||Published - 16 Feb 2010|
- Nuclear factor-κB essential modulator
- Toll-like receptor