Mouse Gene Knockouts

Phenotypes of Mouse Rel/NF-kB/IkB/IKK Knockouts

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 Phenotype Reference
rela Embryonic lethal;

liver apoptosis;

sensitivity to TNF

Beg & Baltimore, 1996
c-rel Impaired T and B cell activation; systemic arthritis resistance Kontgen et al, 1995

Grumont et al, 1998

Campbell et al, 2000

relb Defects in acquired and innate immunity; T-cell infiltration of organs; skin inflammation Burkly et al, 1995

Weih et al, 1995

Freyschmidt et al, 2007

nfkb1 Immune response defects due to abnormal B-cell response; resistance to arthritis; neural degeneration; sleep irregularities Sha et al, 1995

Campbell et al, 2000

Lu et al, 2006; Jhaveri et al, 2006

nfkb2 Abnormal spleen and lymph node architecture; defective T-cell response Caamano et al, 1998

Franzoso et al, 1998

c-rel

delta C

Lymphoid cell hyperplasia Carrasco et al, 1998
nfkb1

delta C

Splenomegaly; enlarged lymph nodes; infiltrations of lung & liver; susceptibility to pathogens Ishikawa et al, 1998
nfkb2

delta C

Multiple post-natal organ defects Ishikawa et al, 1997
nfkb1/relb Lethal 3-4 weeks post-natal;

Increased organ inflammation

Weih et al, 1997
nfkb1/nfkb2 Reduced growth; cranofacial abnormalities; bone defects; B-cell defects Franzoso et al, 1997

Iotsova et al, 1997

nfkb1/c-rel Decreased humoral immunity Pohl et al, 2002
c-rel/rela Embryonic lethal early liver apoptosis; skin epidermus development Grossmann et al, 1999; Gugasyan et al., 2004
ikba Early neonatal lethal inflammatory dermatitis and granulocytosis Beg et al, 1995

Klement et al, 1996

ikbb
ikbe Reduction in number of CDD44-CD25+ T cells Memet et al, 1999
bcl-3 Defects in B- and T-cell responses to antigens Franzoso et al, 1997

Schwartz et al, 1997

IKKa Early neonatal lethal;

Skin defects

Hu et al, 1999

Takeda et al, 1999

IKKb Embryonic lethal;

Liver apoptosis;

Sensitivity to TNF; B-cell survival (conditional)

Li et al, 1999

Takeda et al, 1999

Li et al., 2003

IKKa/IKKb Embryonic lethal;  Liver apoptosis; Sensitivity to TNF; Neural defects Li et al, 2000
IKKg (NEMO) Embryonic lethal;  Liver apoptosis; Sensitivity to TNF; Heterozygotes are model for incontinentia pigmenti Rudolph et al, 2000 Makris et al, 2000