title: Influence of the 5' intron in the control of acetylcholinesterase gene expression during myogenesis.
abstract: During myogenesis, marked increases in both acetylcholinesterase (AChE) and its encoding mRNA are observed. The intron in the AChE gene between non-coding exon 1 [T.L. Rachinsky, S. Camp, Y. Li, T.J. Ekstrom, M. Newton, P. Taylor, Molecular cloning of mouse acetylcholinesterase: tissue distribution of alternatively spliced mRNA species, Neuron 5 (1990) 317-327] and start-site containing exon 2 [A. Mutero, S. Camp, P. Taylor, Promoter elements of the mouse acetylcholinesterase gene, J. Biol. Chem. 270 (4) (1995) 1866-1872] appears to be responsible for the enhanced expression of the enzyme upon myoblast to myotube differentiation. Deletion of a 255 bp sequence within the first intron of the AChE gene abolishes the increase in cell-associated activity observed with differentiation. To study the involvement of the intronic region in post-transcriptional processing of AChE message, we used real time RT-PCR to quantify spliced and unspliced message levels in myoblasts and myotubes. We observe a 200-fold increase of the fully spliced mRNA associated with myotube formation, while the increase in the unspliced mRNA retaining either intron 1 or intron 2 is only 5 to 15-fold. We have generated knockout mice without the conserved region of intron 1. The mice show a phenotype where skeletal muscle, hematopoietic and central nervous system AChE expression differ with the greatest effect existing in the disappearance of skeletal muscle expression [S. Camp, L Zhang, M. Marquez, B. de La Torre, J.M. Long, G. Bucht, P. Taylor, Acetylcholinesterase (AChE) gene modification in transgenic animals: functional consequences of selected exon and regulatory region deletion, VIII IMC Proceedings].
authors.affiliation: Department of Pharmacology, University of California San Diego, La Jolla, CA 92093-0636, USA. adejaco@ucsd.edu <adejaco@ucsd.edu>
authors.forename: Antonella
authors.initials: A
authors.lastname: De Jaco
authors.forename: Shelley
authors.initials: S
authors.lastname: Camp
authors.forename: Palmer
authors.initials: P
authors.lastname: Taylor
mesh_terms: D000110:Acetylcholinesterase / Q000172:deficiency / Q000235:genetics* / Q000378:metabolism; D000818:Animals; D002460:Cell Line; D018507:Gene Expression Regulation, Developmental / Q000235:genetics*; D015971:Gene Expression Regulation, Enzymologic / Q000235:genetics*; D007438:Introns / Q000235:genetics*; D051379:Mice; D018345:Mice, Knockout; D024510:Muscle Development / Q000235:genetics*
chemical_list: D000110:Acetylcholinesterase