Tosaki Hiroko, Kunisada Takahiro, Motohashi Tsutomu, Aoki Hitomi, Yoshida Hisahiro, Kitajima Yasuo
Department of Dermatology, Gifu University School of Medicine, Gifu 501-1194, Japan.
J Invest Dermatol. 2006 May;126(5):1111-8. doi: 10.1038/sj.jid.5700173.
Piebaldism is an autosomal dominant genetic pigmentary disorder, characterized by congenital white hair and patches located on the forehead, anterior trunk, and extremities. Most piebald patients have a mutation of the KIT gene, which encodes a tyrosine kinase receptor involved in pigment cell development. The white hair and patches of such patients are already completely formed at birth and do not usually expand thereafter. This stability of pigmented spots also applies to Kit(W) and Kitl(Sl) mutant mice. However, two novel cases of piebaldism were reported in 2001, in which both mother and daughter having a novel Val620Ala mutation in their KIT gene showed progressive depigmentation. To prepare an animal model of this mutation, to explore undefined functions of KIT signaling for maintaining pigmented melanocytes in the skin or more specifically the integrity of the melanocyte stem cell system in the postnatal skin, we produced transgenic mice expressing Val620Ala Kit. These mice well mimicked the white spotting pattern of patients; however, no change in this pattern was observed after birth, even after increasing the transgene expression by various means. Here, we report the unexpectedly extremely stable maintenance of the melanocyte stem cell system under stringent conditions for KIT signaling.
斑驳病是一种常染色体显性遗传色素沉着障碍，其特征为先天性白发以及位于前额、躯干前部和四肢的白斑。大多数斑驳病患者存在KIT基因突变，该基因编码一种参与色素细胞发育的酪氨酸激酶受体。这类患者的白发和白斑在出生时就已完全形成，之后通常不会扩大。色素沉着斑点的这种稳定性也适用于Kit(W)和Kitl(Sl)突变小鼠。然而，2001年报告了两例新型斑驳病病例，其中母亲和女儿的KIT基因均有新型Val620Ala突变，表现出进行性色素脱失。为制备这种突变的动物模型，以探索KIT信号在维持皮肤中色素沉着黑素细胞或更具体地说是出生后皮肤中黑素细胞干细胞系统完整性方面尚未明确的功能，我们培育了表达Val620Ala Kit的转基因小鼠。这些小鼠很好地模拟了患者的白斑模式；然而，出生后即使通过各种方式增加转基因表达，这种模式也未观察到变化。在此，我们报告在严格的KIT信号条件下黑素细胞干细胞系统意外地极其稳定。
