A mutation of Ikbkg causes immune deficiency without impairing degradation of IκBα
Proceedings of the National Academy of Sciences, 2010•National Acad Sciences
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 …
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 …
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.
National Acad Sciences