histological study of the effects of SMO gene activation in mouse skin

ABSTRACT

Activating mutations in the SMO [smoothened] gene have been isolated from human basal cell carcinoma. Basal cell carcinoma [BCC] is the most common human malignancy worldwide. Modeling this type of malignancy in animals would help in studying this disease in depth. This study was carried out to characterize a mouse model having SMO gene activated in its skin to see whether it will develop BCC and serves as a model for this disease. In this study, a transgenic mouse model was characterized in which SMO gene was only activated in its skin. The specimens were processed for paraffin sections. They were used for haematoxylin and eosin staining, immunostochemical staining by keratin 10, BrdU staining and in situ hybridization to detect Gli1 mRNA. In this model, epidermis is thickened with areas of epidermal down growths invading the underlying dermis, one of the protein markers of BCC[K 10] is expressed, one of the signs of epidermal cell proliferation [increased BrdU incorporation] is displayed and one of the hedgehog signaling pathway-a pathway involved in human basal cell carcinoma-target genes [Gli1] is upregulated. These changes are similar to the changes reported in human basaloid follicular hamartoma, but BCC does not develop even in elderly mice. The results of this study indicate that activation of SMO gene in mouse skin appears to be insufficient for the development of BCC