Gene expression profile of the skin in the 'hairpoor' (HrHp) mice by microarray analysis

Abstract

BackgroundThe transcriptional cofactor, Hairless (HR), acts as one of the key regulators of hair follicle cycling; the loss of function mutations is the cause of the expression of the hairless phenotype in humans and mice. Recently, we reported a new Hr mutant mouse called 'Hairpoor' (HrHp). These mutants harbor a gain of the function mutation, T403A, in the Hr gene. This confers the overexpression of HR and HrHp is an animal model of Marie Unna hereditary hypotrichosis in humans. In the present study, the expression profile of HrHp/HrHp skin was investigated using microarray analysis to identify genes whose expression was affected by the overexpression of HR.ResultsFrom 45,282 mouse probes, differential expressions in 43 (>2-fold), 306 (>1.5-fold), and 1861 genes (>1.2-fold) in skin from HrHp/HrHp mice were discovered and compared with skin from wild-type mice. Among the 1861 genes with a > 1.2-fold increase in expression, further analysis showed that the expression of eight genes known to have a close relationship with hair follicle development, ascertained by conducting real-time PCR on skin RNA produced during hair follicle morphogenesis (P0-P14), indicated that four genes, Wif1, Casp14, Krt71, and Sfrp1, showed a consistent expression pattern with respect to HR overexpression in vivo.ConclusionWif1 and Casp14 were found to be upregulated, whereas Krt71 and Sfrp1 were downregulated in cells overexpressing HR in transient transfection experiments on keratinocytes, suggesting that HR may transcriptionally regulate these genes. Further studies are required to understand the mechanism of this regulation by the HR cofactor.

Downregulation of Foxe1 by HR suppresses Msx1 expression in the hair follicles of HrHpmice

“…Hp homozygote mice and identified genes that were differentially expressed compared with wild-type skin (13). Among these genes, we found that Foxe1, a Forkhead family member, was significantly downregulated in Hr Hp …”

“…Hp mice (0.64-fold expression level compared with that of wild-type mice at P0) (13). In addition, Msx1 was recently classified as a Foxe1 target in the developing epithelial cells of the palatal shelves (20).…”

“…The Secreted Frizzled-related Protein 1 (Sfrp1), which is an upstream inhibitor of WNT, was previously documented as be-http://bmbreports.org ing downregulated by HR overexpression in vivo and in vitro (13). Recently, it has been suggested that SFRP1 expression is induced by MSX1 in neuroblastoma in humans (22).…”

“…Hp mice, the expression of patched homolog 1 (Path1), another Shh-related gene, was increased to 1.43-fold compared with wild-type mice (13), suggesting that HR may affect the Shh signaling pathway. HR also transcriptionally regulates several Wnt signaling associated genes, especially those such as Sostdc1, Sfrp1, Sfrp2, and Wnt Inhibitory Facotr 1 (Wif1), which repress Wnt signaling (8,9,13).…”

“…HR also transcriptionally regulates several Wnt signaling associated genes, especially those such as Sostdc1, Sfrp1, Sfrp2, and Wnt Inhibitory Facotr 1 (Wif1), which repress Wnt signaling (8,9,13). Moreover, the downregulation of these genes by HR causes Wnt pathway induction, which is critical for the proliferation and differentiation of HF cells and cyclic regeneration of the HF (8,9).…”