The W(sh) and Ph mutations affect the c-kit expression profile: c-kit misexpression in embryogenesis impairs melanogenesis in W(sh) and Ph mutant mice Journal Article

   

Authors:	Duttlinger, R.; Manova, K.; Berrozpe, G.; Chu, T. Y.; DeLeon, V.; Timokhina, I.; Chaganti, R. S. K.; Zelenetz, A. D.; Bachvarova, R. F.; Besmer, P.
Article Title:	The W(sh) and Ph mutations affect the c-kit expression profile: c-kit misexpression in embryogenesis impairs melanogenesis in W(sh) and Ph mutant mice
Abstract:	The receptor tyrosine kinases (RTKs) c-kit and platelet-derived growth factor receptor a chain (PDG-FRa) are encoded at the white spotting (W) and patch (Ph) loci on mouse chromosome 5. While W mutations affect melanogenesis, gametogenesis, and hematopoiesis, the Ph mutation affects melanogenesis and causes early lethality in homozygotes. W-sash (W(sh)) is an expression mutation and blocks c-kit expression in certain cell types and enhances c-kit expression in others, including at sites important for early melanogenesis. We have determined the effect of Ph on c-kit expression during embryogenesis in Ph heterozygotes. Immunohistochemical analysis revealed enhanced c-kit expression in several cell types, including sites important for early melanogenesis. We propose that in both W(sh) and Ph mutant mice c- kit misexpression affects early melanogenesis and is responsible for the pigment deficiency. Moreover, we have defined the organization of the RTKs in the W/Ph region on chromosome 5 and characterized the W(sh) mutation by using pulsed-field gel electrophoresis. Whereas the order of the RTK genes was determined as Pdgfra-c-kit-flk1, analysis of the W(sh) mutation revealed that the c-kit and Pdgfra genes are unlinked in W(sh), presumably because of an inversion of a small segment of chromosome 5. The Ph mutation consists of a deletion including Pdgfra and the 3' deletion endpoint of Ph lies between Pdgfra and c-kit. Therefore, positive 5' upstream elements controlling c-kit expression in mast cells and some other cell types are affected by the W(sh) mutation and negative elements are affected by both the W(sh) and the Ph mutation.
Keywords:	immunohistochemistry; platelet derived growth factor; oncoprotein; gene mutation; genetics; mutation; proto-oncogene proteins; nonhuman; molecular genetics; polymerase chain reaction; mouse; animal; mice; gene; stem cell factor receptor; proto oncogene; gene expression; melanin; embryo; embryo development; platelet derived growth factor receptor; protein tyrosine kinase; mice, inbred c57bl; physiology; cell type; pigmentation; biosynthesis; dna; molecular sequence data; nucleotide sequence; base sequence; receptor protein-tyrosine kinases; dna primers; primer dna; mouse strain; melanogenesis; receptors, platelet-derived growth factor; chromosome map; pulsed field gel electrophoresis; chromosome mapping; mast cell; proto-oncogenes; chromosome 5; restriction mapping; colony stimulating factor receptor; priority journal; article; support, u.s. gov't, p.h.s.; dna probe; proto-oncogene protein c-kit; receptors, colony-stimulating factor; proto oncogene protein c kit; proto oncogene proteins; receptor protein tyrosine kinases; receptors, colony stimulating factor; receptors, platelet derived growth factor
Journal Title:	Proceedings of the National Academy of Sciences of the United States of America
Volume:	92
Issue:	9
ISSN:	0027-8424
Publisher:	National Academy of Sciences
Date Published:	1995-04-25
Start Page:	3754
End Page:	3758
Language:	English
DOI:	10.1073/pnas.92.9.3754
PUBMED:	7537375
PROVIDER:	scopus
PMCID:	PMC42040
DOI/URL:	https://www.scopus.com/inward/record.uri?eid=2-s2.0-0028988966&doi=10.1073%2fpnas.92.9.3754&partnerID=40&md5=75d2d2528b21163225ce009d63cdcb48
Notes:	Article -- Export Date: 28 August 2018 -- Source: Scopus

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