Four-kilobase sequence of the mouse CNP gene directs spatial and temporal expression of lacZ in transgenic mice

J Neurosci Res. 1998 Aug 15;53(4):393-404. doi: 10.1002/(SICI)1097-4547(19980815)53:4<393::AID-JNR1>3.0.CO;2-1.


The gene encoding 2',3'-cyclic nucleotide 3'-phosphodiesterase (CNP) is one of the earliest myelin genes to be expressed in the brain. It is expressed at basal levels in some non-neural tissues but at much higher levels in the nervous system, and its relevance and mechanism are unknown. Using transgenic mice, we examined the expression pattern conferred by a 4-kilobase (-kb) 5'-flanking sequence of the mouse CNP gene coupled to the bacterial lacZ reporter gene. Here we report that this 4-kb fragment contains sufficient information to direct expression of the transgene to the tissue and/or cell type, in which CNP is normally expressed. In the central nervous system (CNS), CNP-lacZ expression was regulated in a temporal manner, consistent with endogenous CNP expression. Transgene expression was detected in embryonic brain and spinal cord in immature oligodendrocytes, and it significantly increased with age. In adult mice, beta-galactosidase activity (which appeared to be oligodendrocyte specific) was found essentially in white matter areas of the CNS. Moreover, the transgene was expressed in peripheral nervous system, testis, and thymus-tissues that normally express CNP. Taken together, our results provide strong evidence that cis-acting regulatory elements, necessary to direct spatial and temporal expression of the transgene in oligodendrocytes, are located within the 4-kb 5'-flanking sequence of the mouse CNP gene. This promoter could be a valuable tool to target specific expression of other transgenes to oligodendrocytes, and may provide important new insights into myelination or dysmyelination.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aging
  • Animals
  • Brain / embryology
  • Brain / growth & development
  • Brain / metabolism*
  • Embryonic and Fetal Development
  • Exons
  • Gene Expression Regulation, Enzymologic*
  • Genes, Reporter
  • Male
  • Mice
  • Mice, Transgenic
  • Natriuretic Peptide, C-Type / biosynthesis
  • Natriuretic Peptide, C-Type / genetics*
  • Oligodendroglia / metabolism
  • Organ Specificity
  • Recombinant Fusion Proteins
  • Reverse Transcriptase Polymerase Chain Reaction
  • Spinal Cord / embryology
  • Spinal Cord / growth & development
  • Spinal Cord / metabolism*
  • beta-Galactosidase / biosynthesis
  • beta-Galactosidase / genetics


  • Recombinant Fusion Proteins
  • Natriuretic Peptide, C-Type
  • beta-Galactosidase