A novel P-0 glycoprotein transgene activates expression of lacZ in myelin-forming Schwann cells

P-0 glycoprotein, the most abundant protein in peripheral nerve, is express ed 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 transgen es has been inconsistent. As much as 9 kb of 5' flanking sequence fused to lacZ never yielded detectable levels of beta-galactosidase in multiple line s of mice. We describe transgenic mice that express lacZ in peripheral nerv e, using the complete mouse P-0 gene, including 6 kb of 5' flanking sequenc e, all exons and introns, and the natural polyadenylation signal. This vect or activated lacZ expression specifically in cultured Schwann cells, and my elin-forming Schwann cells in four out of six transgenic lines. Transgene e xpression paralleled that of the endogenous P-0 gene, both during developme nt and after Wallerian degeneration. lacZ expression was lower than endogen ous P-0 expression, and was not detected in neural crest or Schwann cell pr ecursors, 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 res ulting transgenic mRNA was expressed at levels comparable to endogenous P-0 mRNA. These data suggest that intragenic or 3' flanking sequences are nece ssary to generate the remarkable levels of endogenous P-0 gene expression.