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The study investigated the expression of ornithine decarboxylase (ODC) in mouse skin treated with the tumor promoter TPA. It was found that ODC expression was heterogeneous, with high levels predominantly in suprabasal cells around hair follicles shortly after TPA treatment. This expression was transient, disappearing within 16 to 24 hours, but persisted in some cells within benign papillomas a week after TPA application. Pretreatment with retinoic acid or cycloheximide inhibited ODC expression. The findings suggested that both normal and tumor tissues in mice exhibited varied ODC expression.

In this study, researchers investigated the effects of a mutant Adenovirus E1a oncoprotein, NTdl646, on keratinocyte growth and differentiation in transgenic mice. The protein was expressed specifically in the skin using a keratin 5 promoter, resulting in two lines of mice with abnormal hair phenotypes, including short, crooked hair shafts and dystrophic or absent inner root sheaths. Despite these hair follicle maturation disturbances, the interfollicular epidermis remained normal, and there was no increase in spontaneous or chemically induced skin tumors. The study concluded that while the transgene disrupted keratinocyte maturation, it did not lead to increased epidermal proliferation or neoplastic growth.

Elevated ornithine decarboxylase (ODC) activity in the epidermis was found to promote skin tumor development by recruiting hair follicle bulge stem cells, as demonstrated in ODC-ER transgenic mice. The study showed that inducing ODC activity with 4-hydroxytamoxifen (4OHT) was sufficient to recruit these stem cells in quiescent skin. Although increased ODC activity also led to higher reactive oxygen species (ROS) generation, the use of the polyamine catabolic oxidase inhibitor MDL72527 revealed that ROS generation did not contribute to tumorigenesis. Instead, MDL72527 treatment resulted in a shorter tumor latency, increased tumor burden, and more carcinomas, indicating that the recruitment of bulge stem cells, rather than ROS, played a key role in tumor promotion.

The study introduced the rat ornithine transcarbamylase (OTC) gene into OTC-deficient spf-ash mice, resulting in significant improvements in enzyme activity and metabolic markers. Hemizygous spf-ash mice with the transgene exhibited liver OTC activity about twice that of nontransgenic counterparts and small intestinal OTC activity 6 times higher, reaching 12% and 27% of control levels, respectively. These transgenic mice displayed normal hair growth, nearly normalized urinary orotic acid excretion, and normalized serum citrulline concentration, indicating a successful correction of the OTC deficiency.