INUTERO MANIPULATION OF COAT COLOR FORMATION BY A MONOCLONAL ANTI-C-KIT ANTIBODY - 2 DISTINCT WAVES OF C-KIT-DEPENDENCY DURING MELANOCYTE DEVELOPMENT
INUTERO MANIPULATION OF COAT COLOR FORMATION BY A MONOCLONAL ANTI-C-KIT ANTIBODY - 2 DISTINCT WAVES OF C-KIT-DEPENDENCY DURING MELANOCYTE DEVELOPMENT
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DOI：
10.1002/j.1460-2075.1991.tb07744.x
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发表时间：
1991-08-01
期刊：
影响因子：
11.4
通讯作者：
NISHIKAWA, SI
中科院分区：
文献类型：
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作者：
NISHIKAWA, S;KUSAKABE, M;NISHIKAWA, SI
先前对在c - kit基因（显性白斑，W）内有各种突变的小鼠的研究表明，这种酪氨酸激酶受体在黑素细胞、生殖细胞和造血细胞的发育中具有功能性作用。然而，尽管有c - kit基因缺陷的小鼠可供研究，且对c - kit的分子性质有了相当的了解，但在妊娠的哪个阶段c - kit对这些细胞谱系各自的发育是功能性必需的，仍不清楚。为了解决这个问题，我们使用了一种单克隆抗c - kit抗体ACK2，作为c - kit功能的拮抗阻断剂，以干扰胚胎期和出生后黑素细胞的发育。将ACK2皮内注射到怀孕小鼠体内后，它进入胚胎，阻断了黑素细胞的正常发育。这种抑制作用表现为后代毛色的改变。此外，ACK2注射也改变了新生小鼠和成年小鼠的毛色。根据在出生前后不同阶段施用ACK2所产生的毛色模式，得出以下结论：（i）在妊娠中期，在交配后约14.5天左右的一段有限时间内，当一系列导致黑素细胞进入表皮层的事件发生时，c - kit在功能上是必需的；（ii）在出生后的生命中，c - kit是黑素细胞激活所必需的，黑素细胞激活与毛发周期同时发生，毛发周期在第一根毛发新生发育后贯穿一生。
Previous studies on mice bearing various mutations within the c-kit gene, dominant white spotting (W), indicate the functional role of this tyrosine kinase receptor in the development of melanocytes, germ cells and hematopoietic cells. Despite the availability of mice defective in the c-kit gene and a respectable understanding of the molecular nature of c-kit, however, it is not clear at what stage of gestation c-kit is functionally required for the development of each of these cell lineages. To address this question, we have used a monoclonal anti-c-kit antibody, ACK2, as an antagonistic blocker of c-kit function to interfere with the development of melanocytes during embryonic and postnatal life. ACK2 injected intradermally into pregnant mice entered the embryos where it blocked the proper development of melanocytes. This inhibitory effect was manifested as coat color alteration in the offspring. Furthermore, ACK2 injection also altered the coat color of neonatal and adult mice. Based on the coat color patterns produced by ACK2 administration at various stages before or after birth, the following conclusions are drawn: (i) during mid-gestation, c-kit is functionally required during a restricted period around day 14.5 post-coitum when a sequence of events leading to melanocyte entry into the epidermal layer occurs; (ii) during postnatal life, c-kit is required for melanocyte activation which occurs concomitantly with the hair cycle which continues throughout life after neonatal development of the first hair.