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A novel P 0 glycoprotein transgene activates expression of lac Z in myelin‐forming Schwann cells
Author(s) -
Feltri M. Laura,
D'Antonio Maurizio,
Quattrini Angelo,
Numerato Rita,
Arona Marta,
Previtali Stefano,
Chiu ShingYan,
Messing Albee,
Wrabetz Lawrence
Publication year - 1999
Publication title -
european journal of neuroscience
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.346
H-Index - 206
eISSN - 1460-9568
pISSN - 0953-816X
DOI - 10.1046/j.1460-9568.1999.00568.x
Subject(s) - transgene , myelin associated glycoprotein , myelin , genetically modified mouse , glycoprotein , microbiology and biotechnology , chemistry , biology , gene , neuroscience , biochemistry , central nervous system
P 0 glycoprotein, the most abundant protein in peripheral nerve, is expressed specifically in the Schwann cell lineage. Upstream of the rat P 0 gene 1.1 kb of DNA can activate expression of cDNAs specifically in Schwann cells in transgenic mice. However, the expression of P 0 promoter‐based transgenes has been inconsistent. As much as 9 kb of 5′ flanking sequence fused to lacZ never yielded detectable levels of β‐galactosidase in multiple lines of mice. We describe transgenic mice that express lacZ in peripheral nerve, using the complete mouse P 0 gene, including 6 kb of 5′ flanking sequence, all exons and introns, and the natural polyadenylation signal. This vector activated lacZ expression specifically in cultured Schwann cells, and myelin‐forming Schwann cells in four out of six transgenic lines. Transgene expression paralleled that of the endogenous P 0 gene, both during development and after Wallerian degeneration. lacZ expression was lower than endogenous P 0 expression, and was not detected in neural crest or Schwann cell precursors, where low levels of P 0 mRNA are present. However, when the same vector contained a small myc tag instead of the 3.2‐kb lacZ insert, the resulting transgenic mRNA was expressed at levels comparable to endogenous P 0 mRNA. These data suggest that intragenic or 3′ flanking sequences are necessary to generate the remarkable levels of endogenous P 0 gene expression.