Department of Biomedical Sciences, The Catholic University of Korea, 505 Banpo-dong, Seoul 137-701, Korea.
BMC Genomics. 2010 Nov 18;11:640. doi: 10.1186/1471-2164-11-640.
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.
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.
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.
转录共激活因子 Hairless（HR）是毛囊周期的关键调节因子之一；功能丧失突变是导致人类和小鼠出现无毛表型的原因。最近，我们报道了一种新的 Hr 突变小鼠，称为“Hairpoor”（Hr（Hp））。这些突变体在 Hr 基因中携带 T403A 的功能获得性突变。这导致 HR 的过表达，并且 Hr（Hp）是人类 Marie Unna 遗传性少毛症的动物模型。在本研究中，使用微阵列分析研究了 Hr（Hp）/Hr（Hp）皮肤的表达谱，以鉴定受 HR 过表达影响的基因。
从 45282 个小鼠探针中，在 Hr（Hp）/Hr（Hp）小鼠皮肤中发现了 43 个（>2 倍）、306 个（>1.5 倍）和 1861 个（>1.2 倍）基因的差异表达，并与野生型小鼠的皮肤进行了比较。在表达上调>1.2 倍的 1861 个基因中，进一步的分析表明，在毛囊形态发生过程中（P0-P14）产生的皮肤 RNA 进行实时 PCR 分析后，有 8 个与毛囊发育密切相关的基因的表达，表明在体内 HR 过表达的情况下，有 4 个基因（Wif1、Casp14、Krt71 和 Sfrp1）表现出一致的表达模式。
在角质细胞的瞬时转染实验中，发现 Wif1 和 Casp14 上调，而 Krt71 和 Sfrp1 下调，提示 HR 可能转录调节这些基因。需要进一步研究以了解 HR 共激活因子的这种调节机制。
