Transgenic mouse model of cutaneous adnexal tumors
Yusuke Kito1, Chiemi Saigo1, Kurabayashi Atsushi2
1Department of Pathology and Translational Research, Gifu University Graduate School of Medicine, Yanagido 1-1, Gifu 501-1194, Japan.
Abstract:
TMEM207 was first characterized as being an important molecule for the invasion activity of gastric signet-ring cell carcinoma cells. In order to unravel the pathological properties of TMEM207, we generated several transgenic mouse lines, designated C57BL/6-Tg (ITF-TMEM207), in which murine TMEM207 was ectopically expressed under a truncated (by ~200 bp) proximal promoter of the murine intestinal trefoil factor (ITF) gene (also known as Tff3). Unexpectedly, a C57BL/6-Tg (ITF-TMEM207) mouse line exhibited a high incidence of spontaneous intradermal tumors with histopathological features that resembled those of various human cutaneous adnexal tumors. These tumors were found in ~14% female and 13% of male 6- to 12-month-old mice. TMEM207 immunoreactivity was found in hair follicle bulge cells in non-tumorous skin, as well as in cutaneous adnexal tumors of the transgenic mouse. The ITF-TMEM207 construct in this line appeared to be inserted to a major satellite repeat sequence at chromosome 2, in which no definite coding molecule was found. In addition, we also observed cutaneous adnexal tumors in three other C57BL/6-Tg (ITF-TMEM207) transgenic mouse lines. We believe that the C57BL/6-Tg (ITF-TMEM207) mouse might be a useful model to understand human cutaneous adnexal tumors.
Insights
Transgenic mice overexpressing TMEM207 developed spontaneous skin tumors resembling human cutaneous adnexal tumors. This TMEM207 mouse model offers a new tool for studying these complex skin conditions.
Area of Science:
- Oncology
- Genetics
- Dermatology
Background:
- Transmembrane protein 207 (TMEM207) is implicated in gastric cancer invasion.
- Understanding TMEM207's broader pathological roles requires further investigation.
Purpose of the Study:
- To generate and characterize transgenic mouse models for studying TMEM207's pathological properties.
- To investigate the potential of TMEM207 in the development of cutaneous adnexal tumors.
Main Methods:
- Generation of C57BL/6-Tg (ITF-TMEM207) transgenic mouse lines with ectopic TMEM207 expression.
- Histopathological analysis of spontaneous intradermal tumors in transgenic mice.
- Immunohistochemical detection of TMEM207 in skin and tumors.
- Analysis of transgene insertion site.
Main Results:
- One transgenic mouse line exhibited a high incidence of spontaneous intradermal tumors (~14% female, 13% male) in 6- to 12-month-old mice.
- Tumor histopathology resembled various human cutaneous adnexal tumors.
- TMEM207 was detected in hair follicle bulge cells and cutaneous adnexal tumors.
- Three additional transgenic lines also showed cutaneous adnexal tumors.
Conclusions:
- The C57BL/6-Tg (ITF-TMEM207) mouse model spontaneously develops tumors resembling human cutaneous adnexal tumors.
- This transgenic model may serve as a valuable tool for understanding the pathogenesis of human cutaneous adnexal tumors.
- Ectopic TMEM207 expression is linked to the development of these skin tumors.
