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

✍ Scribed by M. Gravel; A. Di Polo; P.B. Valera; P.E. Braun

• Publisher: John Wiley and Sons
• Year: 1998
• Tongue: English
• Weight: 932 KB
• Volume: 53
• Category: Article
• ISSN: 0360-4012
• DOI: 10.1002/(sici)1097-4547(19980815)53:4<393::aid-jnr1>3.0.co;2-1

✦ Synopsis

The gene encoding 2Ј,3Ј-cyclic nucleotide 3Ј-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) 5Ј-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, ␤-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 5Ј-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.