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A Myelin Proteolipid Protein-LacZ Fusion Protein Is Developmentally Regulated and Targeted to the Myelin Membrane in Transgenic Mice

Wight, Patricia A. and Duchala, Cynthia S. and Readhead, Carol and Macklin, Wendy B. (1993) A Myelin Proteolipid Protein-LacZ Fusion Protein Is Developmentally Regulated and Targeted to the Myelin Membrane in Transgenic Mice. Journal of Cell Biology, 123 (2). pp. 443-454. ISSN 0021-9525. http://resolver.caltech.edu/CaltechAUTHORS:20120308-100109187

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Abstract

Transgenic mice were generated with a fusion gene carrying a portion of the murine myelin proteolipid protein (PLP) gene, including the first intron, fused to the E. coli LacZ gene. Three transgenic lines were derived and all lines expressed the transgene in central nervous system white matter as measured by a histochemical assay for the detection of β-galactosidase activity. PLP-LacZ transgene expression was regulated in both a spatial and temporal manner, consistent with endogenous PLP expression. Moreover, the transgene was expressed specifically in oligodendrocytes from primary mixed glial cultures prepared from transgenic mouse brains and appeared to be developmentally regulated in vitro as well. Transgene expression occurred in embryos, presumably in pre- or nonmyelinating cells, rather extensively throughout the peripheral nervous system and within very discrete regions of the central nervous system. Surprisingly, beta-galactosidase activity was localized predominantly in the myelin in these transgenic animals, suggesting that the NH_2-terminal 13 amino acids of PLP, which were present in the PLP-LacZ gene product, were sufficient to target the protein to the myelin membrane. Thus, the first half of the PLP gene contains sequences sufficient to direct both spatial and temporal gene regulation and to encode amino acids important in targeting the protein to the myelin membrane.


Item Type:Article
Related URLs:
URLURL TypeDescription
http://dx.doi.org/10.1083/jcb.123.2.443DOIUNSPECIFIED
http://jcb.rupress.org/content/123/2/443PublisherUNSPECIFIED
Additional Information:© 1993 Rockefeller University Press. Received for publication 19 March 1993 and in revised form 1 July 1993. Published October 15, 1993. The authors thank Dr. Robin Fisher, Director of the Neurohistology Core of the UCLA Mental Retardation Research Center for extensive consultation on the neuroanatomical aspects of transgene expression; Dr. Karl Herrup for discussions on use of LacZ; Janet Miyashiro, Kristine Engelbrecht, Lee Zane, and Svetlana Arutyunovna for excellent technical assistance; and Carol Gray and Sharon Belkin for assistance with the artwork. We thank Dr. Leroy Hood for his encouragement and support. These studies were supported by grants from the National Multiple Sclerosis Society and National Institutes of Health grants NS25304 and HD25831 to W. B. Macklln and AG07687 (C. Readhead). P. A. Wight was supported by a fellowship from the National Institutes of Health (NS08774) and C. S. Duchala by a fellowship from the National Multiple Sclerosis Society.
Funders:
Funding AgencyGrant Number
National Multiple Sclerosis SocietyUNSPECIFIED
NIHNS25304
NIHHD25831
NIHNS08774
National Multiple Sclerosis Society fellowshipUNSPECIFIED
NIHAG07687
Record Number:CaltechAUTHORS:20120308-100109187
Persistent URL:http://resolver.caltech.edu/CaltechAUTHORS:20120308-100109187
Official Citation:A myelin proteolipid protein-LacZ fusion protein is developmentally regulated and targeted to the myelin membrane in transgenic mice. P A Wight, C S Duchala, C Readhead, and W B Macklin 123:443-454. doi:10.1083/jcb.123.2.443
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:29643
Collection:CaltechAUTHORS
Deposited By: Ruth Sustaita
Deposited On:12 Mar 2012 20:45
Last Modified:26 Dec 2012 14:55

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