Constitutive activation of Stat3 in mouse epidermis. Mus musculus

Potential Stat3 target genes involved in hair follicle formation were examined using mouse whole-genome microarray analysis. Global gene expression patterns in the epidermis of transgenic mice with keratinocytes expressing a constitutively active Stat3BK5.Stat3C mice (Sano et al., 2005) were compared with the pattern in the epidermis of wild-type mice. Of approximately 130 differentially expressed genes detected by microarray, approximately 70 genes were significantly up-regulated in epidermis by constitutive activation of Stat3. Thirty three of these genes were hair follicle related genes. These genes included trichohyalin, hair keratins, and keratin-associated proteins that are expressed in the hair shaft and inner root sheath as essential structural components for hair growth (Winter et al., 1997). To confirm the microarray results, five genes whose expression was up-regulated in the epidermis of BK5.Stat3C mice were chosen for quantitative RT-PCR analysis. Consistent with the microarray data, the expression of Tchh, Krtap16-8, Krtap6-1, Krt33a, and Krt25d was significantly increased in the epidermis of BK5.Stat3C mice compared to wild-type mice. In addition, Krtap16-1, which was not identified by microarray analysis but is localized on mouse chromosome 16, was highly expressed in the epidermis of BK5.Stat3C mice in comparison to wild-type (Figure 1f). Overall design: RNA samples were prepared from dorsal epidermis of female FVB mice (control) and BK5.Stat3C mice. Epidermal RNA from two mice from each group was pooled. One microarray hybridization of control vs transgenic was performed for this particular study. All remaining expression analysis was conducted by RT-PCR.