Limb and skin abnormalities in mice lacking IKKalpha.
The gene encoding inhibitor of kappa B (IkappaB) kinase alpha (IKKalpha; also called IKK1) was disrupted by gene targeting. IKKalpha-deficient mice died perinatally. In IKKalpha-deficient fetuses, limb outgrowth was severely impaired despite unaffected skeletal development. The epidermal cells in IKKalpha-deficient fetuses were highly proliferative with dysregulated epidermal differentiation. In the basal layer, degradation of IkappaB and nuclear localization of nuclear factor kappa B (NF-kappaB) were not observed. Thus, IKKalpha is essential for NF-kappaB activation in the limb and skin during embryogenesis. In contrast, there was no impairment of NF-kappaB activation induced by either interleukin-1 or tumor necrosis factor-alpha in IKKalpha-deficient embryonic fibroblasts and thymocytes, indicating that IKKalpha is not essential for cytokine-induced activation of NF-kappaB.
Takeda
K
K
Department of Biochemistry and Core Research for Evolutional Science and Technology (CREST), Japan Science and Technology Corporation, Department of Pathology, Hyogo College of Medicine, 1-1 Mukogawa-cho, Nishinomiya, Hyogo 663-8501, Japan.
Takeuchi
O
O
Tsujimura
T
T
Itami
S
S
Adachi
O
O
Kawai
T
T
Sanjo
H
H
Yoshikawa
K
K
Terada
N
N
Akira
S
S
D000818:Animals; D002454:Cell Differentiation; D003593:Cytoplasm / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000378:metabolism; D000078404:Epidermal Cells; D004817:Epidermis / Q000196:embryology* / Q000378:metabolism; D005121:Extremities / Q000196:embryology* / Q000254:growth & development; D018507:Gene Expression Regulation, Developmental; D018390:Gene Targeting; D051550:I-kappa B Kinase; D020672:I-kappa B Proteins; D007375:Interleukin-1 / Q000494:pharmacology; D015603:Keratinocytes / Q000166:cytology / Q000378:metabolism; D018878:Limb Buds / Q000201:enzymology; D017880:Limb Deformities, Congenital / Q000201:enzymology* / Q000235:genetics; D051379:Mice; D018006:Myogenic Regulatory Factors; D016328:NF-kappa B / Q000378:metabolism; D009687:Nuclear Proteins / Q000235:genetics; D010766:Phosphorylation; D017346:Protein Serine-Threonine Kinases / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D012868:Skin Abnormalities / Q000201:enzymology* / Q000235:genetics; D051996:Transcription Factor RelA; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology; D051879:Twist-Related Protein 1
D004268:DNA-Binding Proteins; D020672:I-kappa B Proteins; D007375:Interleukin-1; D018006:Myogenic Regulatory Factors; D016328:NF-kappa B; D009687:Nuclear Proteins; D051996:Transcription Factor RelA; D014409:Tumor Necrosis Factor-alpha; D051879:Twist-Related Protein 1; C067250:Twist1 protein, mouse; D017346:Protein Serine-Threonine Kinases; C496564:Chuk protein, mouse; D051550:I-kappa B Kinase; C496562:Ikbkb protein, mouse; C496566:Ikbke protein, mouse