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INUTERO MANIPULATION OF COAT COLOR FORMATION BY A MONOCLONAL ANTI-C-KIT ANTIBODY - 2 DISTINCT WAVES OF C-KIT-DEPENDENCY DURING MELANOCYTE DEVELOPMENT
Author(s): NISHIKAWA S, KUSAKABE M, YOSHINAGA K, OGAWA M, HAYASHI SI, KUNISADA T, ERA T, SAKAKURA T, NISHIKAWA SI
Source: EMBO JOURNAL    Volume: 10    Issue: 8    Pages: 2111-2118    Published: AUG 1991  
Times Cited: 377     References: 31     
Abstract: 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.
Document Type: Article
Language: English
Reprint Address: NISHIKAWA, S (reprint author), KUMAMOTO UNIV, SCH MED, INST MED IMMUNOL, DEPT PATHOL, HONJO 2-2-1, KUMAMOTO 860, JAPAN
Addresses:
1. INST PHYS & CHEM RES, TSUKUBA LIFE SCI CTR, CELL BIOL LAB, TSUKUBA, IBARAKI 305 JAPAN
2. KUMAMOTO UNIV, SCH MED, DEPT ANAT, KUMAMOTO 860, JAPAN
Publisher: OXFORD UNIV PRESS UNITED KINGDOM, WALTON ST JOURNALS DEPT, OXFORD, ENGLAND OX2 6DP
Subject Category: Biochemistry & Molecular Biology; Cell Biology
IDS Number: FW473
ISSN: 0261-4189
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