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首页> 外文期刊>Pigment cell research >Skin layer-specific transcriptional profiles in normal and recessive yellow (Mc1r(e)/Mc1r(e)) mice
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Skin layer-specific transcriptional profiles in normal and recessive yellow (Mc1r(e)/Mc1r(e)) mice

机译：正常和隐性黄色（Mc1r（e）/ Mc1r（e））小鼠的皮肤层特异性转录谱

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The melanocortin 1 receptor (Mc1r) plays a central role in cutaneous biology, but is expressed at very low levels by a small fraction of cells in the skin. In humans, loss-of-function MC1R mutations cause fair skin, freckling, red hair, and increased predisposition to melanoma; in mice, Mc1r loss-of-function is responsible for the recessive yellow mutation, associated with pheomelanic hair and a decreased number of epidermal melanocytes. To better understand how Mc1r signaling affects different cutaneous phenotypes, we examined large-scale patterns of gene expression in different skin components (whole epidermal sheets, basal epidermal cells and whole skins) of neonatal (P2.5) normal and recessive yellow mice, starting with a 26K mouse cDNA microarray. From c. 17 000 genes whose levels could be accurately measured in neonatal skin, we identified 883, 2097 and 552 genes that were uniquely expressed in the suprabasal epidermis, basal epidermis and dermis, respectively; specific biologic roles could be assigned for each class. Comparison of normal and recessive yellow mice revealed 69 differentially expressed genes, of which the majority had not been previously implicated in Mc1r signaling. Surprisingly, many of the Mc1r-dependent genes are expressed in cells other than melanocytes, even though Mc1r expression in the skin is confined almost exclusively to epidermal melanocytes. These results reveal new targets for Mc1r signaling, and point to a previously unappreciated role for a Mc1r-dependent paracrine effect of melanocytes on other components of the skin.
机译：黑皮质素1受体（Mc1r）在皮肤生物学中起着核心作用，但在皮肤中仅一小部分细胞以极低的水平表达。在人类中，功能丧失的MC1R突变会导致皮肤白皙，雀斑，红发，并易患黑色素瘤。在小鼠中，Mc1r功能丧失是隐性黄色突变的原因，该突变与浅褐色的头发和表皮黑素细胞数量减少有关。为了更好地了解Mc1r信号传导如何影响不同的皮肤表型，我们检查了新生（P2.5）正常和隐性黄色小鼠的不同皮肤成分（整个表皮层，基底表皮细胞和整个皮肤）中基因表达的大规模模式，从开始用26K小鼠cDNA微阵列。从c。可以准确测量新生儿皮肤水平的17000个基因，我们鉴定出分别在基底上表皮，基底表皮和真皮中唯一表达的883、2097和552个基因;可以为每个班级分配特定的生物学角色。正常小鼠和隐性黄色小鼠的比较显示了69个差异表达的基因，其中大多数以前未与Mc1r信号传导有关。出乎意料的是，许多Mc1r依赖性基因在黑素细胞以外的细胞中表达，即使皮肤中的Mc1r表达几乎只限于表皮黑素细胞。这些结果揭示了Mc1r信号传导的新靶标，并指出了黑素细胞对皮肤其他成分的Mc1r依赖性旁分泌作用的先前未曾意识到的作用。

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