54 citations,
May 2001 in “Journal of Investigative Dermatology” 43 citations,
February 1999 in “Biochemical Journal” The study involved generating a transgenic mouse line overexpressing the SSAT gene under a mouse metallothionein I promoter, leading to significant changes in tissue polyamine pools and delayed permanent hair loss compared to previous models. The liver was notably affected, with altered polyamine levels. Despite high SSAT mRNA levels, enzyme activity was only moderately increased unless induced by ZnSO4 or the polyamine analogue DENSPM, which caused a dramatic increase in enzyme activity and depletion of liver polyamines, resulting in high mortality and liver damage. The findings suggested that SSAT overexpression made the mice highly sensitive to polyamine analogues, indicating a post-transcriptional regulation mechanism.
124 citations,
July 1997 in “Journal of Biological Chemistry” In this study, researchers created a transgenic mouse line that overexpressed spermidine/spermine N^1-acetyltransferase, leading to significant alterations in tissue polyamine pools. These changes included the presence of N^1-acetylspermidine, an unusual accumulation of putrescine, and reduced levels of spermidine and spermine. The most notable phenotypic effect was permanent hair loss in mice aged 3 to 4 weeks, associated with the formation of follicular cysts in the dermis, likely due to putrescine's interference with hair follicle cell differentiation and proliferation. Additionally, female mice were infertile, linked to ovarian hypofunction and underdeveloped uteri. This research highlighted the potential of using spermidine/spermine N^1-acetyltransferase overexpression to manipulate polyamine levels in transgenic animals for studying developmental and cancer-related outcomes.
71 citations,
May 1996 in “Journal of Investigative Dermatology” The study investigated the role of ornithine decarboxylase (ODC) in hair follicle function using transgenic mice that overexpressed a mutated ODC transgene in hair follicle keratinocytes. These mice experienced normal initial hair growth but lost their hair completely 2-3 weeks after birth, coinciding with the onset of ODC overexpression and the development of follicular cysts. The study found that the ODC inhibitor 2-difluoromethylornithine could prevent hair loss and partially restore normal skin histology if administered early, and it could also reactivate hair growth in mice with complete hair loss. The results suggested that ODC played a crucial regulatory role in mouse hair follicles.
33 citations,
March 1994 in “PubMed” The study investigated the expression patterns of ornithine decarboxylase (ODC) and keratins in early papillomas in SENCAR mice to identify markers for early skin tumorigenesis. Tumors were induced using 7,12-dimethylbenzanthracene and promoted with 12-O-tetradecanoylphorbol-13-acetate. In early papillomas, keratin K1 showed patchy staining, while K10 was minimally expressed, contrasting with their normal expression in mildly hyperplastic epidermis. ODC expression was intense and diffuse in suprabasal cells of papillomas, correlating with decreased K1 and K10 expression, indicating altered differentiation. These findings suggested that high ODC expression and reduced K1 and K10 could serve as markers for early tumorigenesis in mouse skin.
