Nucleic Acids Research, 1994, Vol. 22, No. 22 4748-4755
© 1994
MOLECULAR BIOLOGY |
The presence of both negative and positive elements in the 5'-flanking sequence of the rat Na, K-ATPase 
3 subunit gene are required for brain expression in transgenic mice
Department of Molecular Genetics, Biochemistry and Microbiology, University of Cincinnati College of Medicine Cincinnati, OH 45267-0524, USA
*To whom correspondence should be addressed
Received June 22, 1994. Revised September 13, 1994. Accepted September 13, 1994.
The Na, K-ATPase is an integral plasma membrane protein consisting of 
and ß subunits, each of which has discrete isoforms expressed in a tissue-specific manner. Of the three functional isoform genes, the one encoding the 3 isoform is the most tissuerestricted in its expression, being found primarily in the brain. To identify regions of the 3 isoform gene that are involved in directing expression in the brain, a 1.6 kb 5'-flanking sequence was attached to a reporter gene, chloramphenicol acetyltransferase (CAT). The 3 – CAT chimeric gene construct was microinjected into fertilized mouse eggs, and transgenic mice were produced. Analysis of adult transgenic mice from different lines revealed that the transgene is expressed primarily in the brain. To further delineate regions that are needed for conferring expression in this tissue, systematic deletions of the 5'-f lanking sequence of the 3–CAT fusion constructs were made and analyzed, again using transgenic mice. The results from these analyses indicate that DNA sequences required for mediating brain-specific expression of the 3 isoform gene are present within 210 bp upstream of the transcription initiation site. 3-CAT promoter constructs containing scanning mutations in this region were also assayed in transgenic mice. These studies have identified both a functional neural-restrictive silencer element as well as a positively acting cis element.
+Present address: Mammalian Genetics Laboratory, ABL–Basic Research Program, NCI–Frederick Cencer Research and Development Center, Frederick, MD 21702, USA
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