Histological studies on eyelid opening in normal male mice and hemizygotes for the mutant gene Tabby (Ta) with and without epidermal growth factor treatment.

Previous work has shown that mice hemizygous or homozygous for the mutant gene Tabby have delayed eyelid opening, as compared to unaffected, wildtype littermate controls; exogenous treatment with epidermal growth factor reverses this delay. We performed histological studies to explore the mechanisms of action of the Tabby gene and of epidermal growth factor in these processes. These show that eyelid opening is associated with keratinization of the fusion junction and conjunctival sac formation. Both these processes occur earlier in normal male mice (days 4 and 7 respectively) than in Tabby hemizygotes (days 7 and 10, respectively). After epidermal growth factor injection, keratinization and conjunctival sac formation are both observed on postnatal day 1 in all control and mutant pups. Thus epidermal growth factor appears to accelerate eyelid opening by stimulating these morphological processes and the Tabby gene appears to delay eyelid opening by impairing them. It is possible that deficiency of epidermal growth factor at the tissue level may be involved in the development of some of the traits seen in Tabby mutants. In addition to analysing the effects of the Tabby gene and of epidermal growth factor on eyelid opening in the mouse, this study appears to be the first detailed histological description of normal eyelid opening. The findings have potential clinical significance; firstly, because the Tabby gene shows genetic homology to the human gene for hypohidrotic ectodermal dysplasia, and disturbed eyelid opening is a trait of some forms of human ectodermal dysplasia, and secondly, because the gene for epidermal growth factor receptor is an oncogene.