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

Abstract

BACKGROUND: The 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' (Hr(Hp)). These mutants harbor a gain of the function mutation, T403A, in the Hr gene. This confers the overexpression of HR and Hr(Hp) is an animal model of Marie Unna hereditary hypotrichosis in humans. In the present study, the expression profile of Hr(Hp)/Hr(Hp) skin was investigated using microarray analysis to identify genes whose expression was affected by the overexpression of HR. RESULTS: From 45,282 mouse probes, differential expressions in 43 (>2-fold), 306 (>1.5-fold), and 1861 genes (>1.2-fold) in skin from Hr(Hp)/Hr(Hp) 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. CONCLUSION: Wif1 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.