QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text (PDF) References Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Ray, P Articles by Besmer, P Search for Related Content PubMed PubMed Citation Articles by Ray, P Articles by Besmer, P Social Bookmarking                   What's this?

Research Papers

Ectopic expression of a c-kitW42 minigene in transgenic mice: recapitulation of W phenotypes and evidence for c-kit function in melanoblast progenitors.

Molecular Biology Program, Sloan Kettering Institute, New York, New York.

Abstract

The proto-oncogene c-kit encodes a transmembrane tyrosine kinase receptor that is allelic with the murine white-spotting locus (W). W mutations affect melanogenesis, gametogenesis, and hematopoiesis during development and adult life, and they result from the partial or complete loss of c-kit function. The W42 allele is a W mutation with severe effects in both the homozygous and the heterozygous states. Previous analysis of the W42 allele identified a missense mutation in an essential amino acid of the c-kitW42 kinase domain that abolishes the in vitro kinase activity of the c-kitW42 protein but does not affect its normal expression. These results suggested that the c-kitW42 allele was a dominant negative mutation within the context of c-kit-mediated signal transduction. To further explore the dominant negative characteristics of the W42 mutation, we have generated transgenic mice in which ectopic expression is driven by the human beta-actin promoter (hAP). Two mouse lines carrying the hAP-c-kitW42 transgene show an effect on pigmentation and the number of tissue mast cells. The patchy coat color pattern of the line 695 mice may reflect variable expression of the transgene in melanoblast progenitors and their descendants and, consequently, is indicative of a function for c-kit in early melanoblasts. Germ cell development and erythropoiesis, however, do not appear to be affected by the transgene. Mice expressing the c-kitW42 transgene therefore recapitulate some of the phenotypes of mice with W mutations. These results are therefore in agreement with the molecular basis of the W42 mutation and the dominant-negative characteristics of the c-kitW42 protein product.

CiteULike

Connotea

Del.icio.us

Digg

Reddit

Technorati

This article has been cited by other articles:

				N. Kaminski, J. A. Belperio, P. B. Bitterman, L. Chen, S. W. Chensue, A. M.K. Choi, S. Dacic, J. H. Dauber, R. M. du Bois, J. J. Enghild, et al. Idiopathic Pulmonary Fibrosis Am. J. Respir. Cell Mol. Biol., September 1, 2003; 29(3): S1 - 105. [Full Text] [PDF]

				P. Ray, Y. Devaux, D. B. Stolz, M. Yarlagadda, S. C. Watkins, Y. Lu, L. Chen, X.-f. Yang, and A. Ray Inducible expression of keratinocyte growth factor (KGF) in mice inhibits lung epithelial cell death induced by hyperoxia PNAS, May 13, 2003; 100(10): 6098 - 6103. [Abstract] [Full Text] [PDF]

				K. M. Kriauciunas, M. G. Myers Jr., and C. R. Kahn Cellular Compartmentalization in Insulin Action: Altered Signaling by a Lipid-Modified IRS-1 Mol. Cell. Biol., September 15, 2000; 20(18): 6849 - 6859. [Abstract] [Full Text]

				V. C. Broudy, N. L. Lin, H.-J. Buhring, N. Komatsu, and T. J. Kavanagh Analysis of c-kit Receptor Dimerization by Fluorescence Resonance Energy Transfer Blood, February 1, 1998; 91(3): 898 - 906. [Abstract] [Full Text] [PDF]

				D J Dumont, G Gradwohl, G H Fong, M C Puri, M Gertsenstein, A Auerbach, and M L Breitman Dominant-negative and targeted null mutations in the endothelial receptor tyrosine kinase, tek, reveal a critical role in vasculogenesis of the embryo. Genes & Dev., August 15, 1994; 8(16): 1897 - 1909. [Abstract] [PDF]

				S. D. Khare, I. Sarosi, X.-Z. Xia, S. McCabe, K. Miner, I. Solovyev, N. Hawkins, M. Kelley, D. Chang, G. Van, et al. Severe B cell hyperplasia and autoimmune disease in TALL-1 transgenic mice PNAS, March 28, 2000; 97(7): 3370 - 3375. [Abstract] [Full Text] [PDF]