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IkappaB kinase alpha is essential for development of the mammalian cornea and conjunctiva
1Laboratory of Gene Regulation and Signal Transduction, Department of Pharmacology, University of California San Diego, La Jolla, USA. kyoshida@med.hokudai.ac.jp
Purpose:
To determine the requirement of IkappaB kinase alpha (Ikkalpha) for differentiation of the mammalian cornea and conjunctiva.
Methods:
Newborn mice or surgically removed embryonic day (E)18 to E19 fetuses of wild-type and IKK:alpha(-/-) mice were analyzed by light microscopy and electron microscopy or immunocytochemistry using anti-keratin (K)12, K4, K5, IkappaB, or nuclear factor (NF)-kappaB (p50) antibody.
Results:
In the IKKalpha(-/-) eyes, the epithelium of the cornea and the conjunctiva consisted of poorly differentiated cells with round nuclei. K5 was much stronger in the conjunctiva of the IKKalpha(-/-) mice. Expression of K12 in the cornea and K4 in the conjunctiva was impaired in the IKKalpha(-/-) mice. IkappaB expression was low in epithelium of the cornea and conjunctiva of the wild type mice but was very strong in that of the IKKalpha(-/-) mice. During normal development of the conjunctiva, nuclear localization of p50 was seen in areas where basal undifferentiated cells give rise to differentiated cell types, marked by expression of cK4. However, in the IKK++alpha(-/-) tissues, no nuclear p50 staining was detected.
Conclusions:
IKKalpha is specifically required for formation of cornea and conjunctiva. This function may be exerted through an effect on NF-kappaB activity.