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Cloning and chromosomal mapping of the murine norepinephrine transporter. J Neurochem 1998 Jun;70(6):2241-51

Date

05/29/1998

Pubmed ID

9603188

DOI

10.1046/j.1471-4159.1998.70062241.x

Abstract

The norepinephrine (NE) transporter (NET), a target of many clinically prescribed antidepressants, regulates noradrenergic neurotransmission by efficiently clearing NE from synaptic spaces after release. To advance our understanding of NET gene structure, regulation, and potential associations with complex behavioral trait loci, we amplified a mouse norepinephrine transporter (mNET) cDNA from placenta total RNA and utilized mNET probes to isolate and characterize the mNET gene. Inferred translation of the major open reading frame of the mNET cDNA predicts a 617-amino acid protein with 12 putative membrane-spanning regions and 94% identity to human NET. The coding exons of the mNET cDNA were found to be spread across >36 kb of 129/Svj genomic DNA, with exon-intron boundaries bearing consensus gt/ag splice sites. Sequence upstream (202 bp) of the inferred translation initiation site matched the sequence of 5' rapid amplification of cDNA ends products from brain mRNA with no evidence for intervening introns and is preceded by a TATA box and canonical transcriptional regulatory elements that may play a role in mNET expression in vivo. Probes derived from mNET cDNA identified species-specific MspI restriction fragment length variations within the mNET gene that were utilized to position the gene (Slc6a5) to murine chromosome 8, one recombinant distal to D8Mit15. This site is within a recently defined quantitative trait locus defined for ethanol sensitivity in LSXSS recombinant inbred mice, Lore4. The status of Slc6a5 as a candidate gene for alcohol sensitivity is discussed with respect to studies noting ethanol-induced alterations in brain NE receptors, NE receptor-linked adenylate cyclase, and NE transport.

Author List

Fritz JD, Jayanthi LD, Thoreson MA, Blakely RD

Author

Jeffery Duane Fritz PhD Associate Professor in the Medical School Regional Campuses department at Medical College of Wisconsin




MESH terms used to index this publication - Major topics in bold

Amino Acid Sequence
Animals
Base Sequence
Carrier Proteins
Cattle
Chromosome Mapping
Cloning, Molecular
DNA, Complementary
Exons
Humans
Introns
Mice
Molecular Sequence Data
Norepinephrine
Norepinephrine Plasma Membrane Transport Proteins
Placenta
Polymerase Chain Reaction
Rana catesbeiana
Rats
Species Specificity
Symporters