Targeted disruption of MAIL, a nuclear IkappaB protein, leads to severe atopic dermatitis-like disease.
MAIL (molecule-possessing ankyrin repeats induced by lipopolysaccharide) is a nuclear IkappaB protein that is also termed interleukin-1-inducible nuclear ankyrin repeat protein or inhibitor of nuclear factor kappaB (IkappaB) zeta. In this study, we generated Mail-/- mice to investigate the roles of MAIL in whole organisms. Mail-/- mice grew normally until 4-8 weeks after birth, when they began to develop lesions in the skin of the periocular region, face, and neck. MAIL mRNA and protein were constitutively expressed in the skin of wild type controls, especially in the keratinocytes. Serum IgE was higher in Mail-/- mice than in normal. Histopathological analysis indicated that the Mail-/- skin lesions appeared to be atopic dermatitis (AD) eczema with inflammatory cell infiltration. In addition, markedly elevated expression of some chemokines such as thymus and activation-regulated chemokine was detected in the Mail-/- skin lesions, similar to that observed in the skin of patients with AD. In Mail-/- mice, MAIL-deficient keratinocytes might be activated to produce chemokines and induce intraepidermal filtration of inflammatory cells, resulting in the onset of the AD-like disease. These findings suggest that MAIL is an essential molecule for homeostatic regulation of skin immunity. The Mail-/- mouse is a valuable new animal model for research on AD.
Shiina
Takahiko
T
Department of Veterinary Physiology, Faculty of Agriculture, Iwate University, Ueda 3-18-8, Morioka 020-8550, Japan.
Konno
Akihiro
A
Oonuma
Toshina
T
Kitamura
Hiroshi
H
Imaoka
Koichi
K
Takeda
Naoki
N
Todokoro
Kazuo
K
Morimatsu
Masami
M
D048868:Adaptor Proteins, Signal Transducing; D000483:Alleles; D000818:Animals; D017487:Ankyrins / Q000737:chemistry; D018925:Chemokines / Q000378:metabolism; D003876:Dermatitis, Atopic / Q000235:genetics* / Q000378:metabolism; D004195:Disease Models, Animal; D005822:Genetic Vectors; D016678:Genome; D020672:I-kappa B Proteins / Q000737:chemistry; D007073:Immunoglobulin E / Q000097:blood / Q000378:metabolism; D007150:Immunohistochemistry; D007249:Inflammation / Q000378:metabolism; D007515:Islets of Langerhans / Q000166:cytology; D015603:Keratinocytes / Q000378:metabolism; D007633:Keratins / Q000737:chemistry; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D008957:Models, Genetic; D009687:Nuclear Proteins / Q000235:genetics* / Q000502:physiology*; D012333:RNA, Messenger / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D019076:Transgenes
D048868:Adaptor Proteins, Signal Transducing; D017487:Ankyrins; D018925:Chemokines; D020672:I-kappa B Proteins; C417234:NFKBIZ protein, human; D009687:Nuclear Proteins; D012333:RNA, Messenger; D007073:Immunoglobulin E; D007633:Keratins