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Most of the genes encoding the transcription factors (Rel/NF-kB), inhibitors (IkB), and kinases (IKK) in the Rel/NF-kB signal transduction pathway have been disrupted in mice.These gene knockouts lead to a variety of phenotypes, which are summarized in the table below.There are also links to the primary references for this information, as on PubMed. Gene rela c-rel relb nfkb1 nfkb2 c-rel delta C nfkb1 delta C nfkb2 delta C nfkb1/relb nfkb1/nfkb2 nfkb1/c-rel c-rel/rela ikba Phenotype Reference Embryonic lethal; Beg & Baltimore, 1996 liver apoptosis; sensitivity to TNF Impaired T and B cell Kontgen et al, 1995 activation; systemic arthritis Grumont et al, 1998 resistance Campbell et al, 2000 Defects in acquired and innate Burkly et al, 1995 immunity; T-cell infiltration Weih et al, 1995 of organs; skin inflammation Freyschmidt et al, 2007 Immune response defects due Sha et al, 1995 to abnormal B-cell response; Campbell et al, 2000 resistance to arthritis; neural degeneration; sleep Lu et al, 2006; Jhaveri et al, irregularities 2006 Abnormal spleen and lymph Caamano et al, 1998 node architecture; defective Franzoso et al, 1998 T-cell response Lymphoid cell hyperplasia Carrasco et al, 1998 Splenomegaly; enlarged Ishikawa et al, 1998 lymph nodes; infiltrations of lung & liver; susceptibility to pathogens Multiple post-natal organ Ishikawa et al, 1997 defects Lethal 3-4 weeks post-natal; Weih et al, 1997 Increased organ inflammation Reduced growth; cranofacial abnormalities; bone defects; B-cell defects Decreased humoral immunity Embryonic lethal early liver apoptosis; skin epidermus development Early neonatal lethal inflammatory dermatitis and granulocytosis Franzoso et al, 1997 Iotsova et al, 1997 Pohl et al, 2002 Grossmann et al, 1999; Gugasyan et al., 2004 Beg et al, 1995 Klement et al, 1996 ikbb ikbe bcl-3 IKKa IKKb IKKa/IKKb IKKg (NEMO) Reduction in number of CDD44-CD25+ T cells Defects in B- and T-cell responses to antigens Early neonatal lethal; Skin defects Embryonic lethal; Liver apoptosis; Sensitivity to TNF; B-cell survival (conditional) Embryonic lethal; Liver apoptosis; Sensitivity to TNF; Neural defects Embryonic lethal; Liver apoptosis; Sensitivity to TNF; Heterozygotes are model for incontinentia pigmenti Memet et al, 1999 Franzoso et al, 1997 Schwartz et al, 1997 Hu et al, 1999 Takeda et al, 1999 Li et al, 1999 Takeda et al, 1999 Li et al., 2003 Li et al, 2000 Rudolph et al, 2000 Makris et al, 2000