Cloning of the Rat Gene Encoding Choline Acetyltransferase, a Cholinergic Neuron-Specific Marker

• Published in: Proceedings of the National Academy of Sciences - PNAS 1992-05, Vol.89 (10), p.4387-4391
• Main Authors: Hahn, Mounou, Hahn, Soonjung L., Stone, Donna M., Joh, Tong H.
• Format: Article
• Language: English
• Subjects: Alzheimer's disease; Amino Acid Sequence; Animals; Bacteriophages; Base Sequence; Binding Sites; Biological and medical sciences; Biomarkers; Blotting, Southern; Brain; choline acetyltransferase; Choline O-Acetyltransferase - genetics; Cholinergics; Cloning, Molecular; Codon - genetics; Complementary DNA; DNA Probes; Exons; Fundamental and applied biological sciences. Psychology; Gene Library; Genes; Genes. Genome; Genetics; Genomics; Medical research; Molecular and cellular biology; Molecular genetics; Molecular Sequence Data; Neurons; Neurons - physiology; nucleotide sequence; Polymerase Chain Reaction - methods; predictions; Rats; Rats, Inbred Strains; Restriction Mapping; RNA; Rodents; Spinal cord; TATA Box; Transcription Factors - metabolism
• ISSN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.89.10.4387

The neurotransmitter acetylcholine is synthesized by choline acetyltransferase (ChAT; EC 2.3.1.6). Since the expression of ChAT in the nervous system is restricted to cholinergic neurons, it serves as a specific marker for these neurons. In Alzheimer disease, ChAT activity is markedly reduced in the affected brain areas. Nerve growth factor can increase the ChAT activity of brain cholinergic neurons in vitro and in vivo. We have cloned the rat ChAT gene and identified one 5' noncoding exon and 14 exons that account for the entire coding sequence. The exon organization is compared with the protein domains conserved during evolution. These exons are distributed over at least 64 kilobases in the rat genome; the largest intron is at least 14 kilobases long. Within a 0.7-kilobase region immediately upstream of the confirmed sequence of the noncoding exon, TATA-like elements and numerous potential binding sites for transcription factors are found, including AP-1, Sp1, octamer-binding factor(s), CTF/NF-1, and the nuclear oncoprotein Myb.