Tachibana Masayoshi, Kobayashi Yasuhito, Matsushima Yoshibumi
Research Division, Saitama Cancer Center, Komuro, Ina, Saitama, Japan.
Pigment Cell Res. 2003 Oct;16(5):448-54. doi: 10.1034/j.1600-0749.2003.00066.x.
Waardenburg syndrome (WS) is an auditory-pigmentary syndrome caused by a deficiency of melanocytes and other neural crest-derived cells. Depending on a variety of symptoms associated with the auditory-pigmentary symptoms, WS is classified into four types: WS type 1 (WS1), WS2, WS3, and WS4. Six genes contributing to this syndrome--PAX3, SOX10, MITF, SLUG, EDN3 and EDNRB--have been cloned so far, all of them necessary for normal development of melanocytes. Mutant mice with coat color anomalies were helpful in identifying these genes, although the phenotypes of these mice did not necessarily perfectly match those of the four types of WS. Here we describe mice with mutations of murine homologs of WS genes and verify their suitability as models for WS with special interest in the cochlear disorder. The mice include splotch (Sp), microphthalmia (mi), Slugh-/-, WS4, JF1, lethal-spotting (ls), and Dominant megacolon (Dom). The influence of genetic background on the phenotypes of mice mutated in homologs of WS genes is also addressed. Finally, possible interactions among the six WS gene products are discussed.
瓦登伯革氏综合征（WS）是一种由黑素细胞和其他神经嵴衍生细胞缺乏引起的听觉色素综合征。根据与听觉色素症状相关的各种症状，WS分为四种类型：1型瓦登伯革氏综合征（WS1）、WS2、WS3和WS4。迄今为止，已克隆出六个与该综合征相关的基因——PAX3、SOX10、MITF、SLUG、EDN3和EDNRB——所有这些基因都是黑素细胞正常发育所必需的。毛色异常的突变小鼠有助于鉴定这些基因，尽管这些小鼠的表型不一定与四种类型的WS完全匹配。在此，我们描述了具有WS基因小鼠同源物突变的小鼠，并验证了它们作为WS模型的适用性，特别关注耳蜗疾病。这些小鼠包括斑点（Sp）、小眼症（mi）、Slugh-/-、WS4、JF1、致死斑点（ls）和显性巨结肠（Dom）。我们还讨论了遗传背景对WS基因同源物突变小鼠表型的影响。最后，讨论了六种WS基因产物之间可能的相互作用。
