Involucrin is synthesized in abundance during terminal differentiation of k
eratinocytes. Involucrin is a substrate for transglutaminase and one of the
precursors of the cross-linked envelopes present in the corneocytes of the
epidermis and other stratified squamous epithelia. These envelopes make an
important contribution to the physical resistance of the epidermis. We hav
e generated mice lacking involucrin from embryonic stem cells whose involuc
rin gene had been ablated by homologous recombination. These mice developed
normally, possessed apparently normal epidermis and hair follicles, and ma
de cornified envelopes that could not be distinguished from those of wild-t
ype mice. No compensatory increase of mRNA for other envelope precursors wa
s observed.