Acetylcholinesterase (AChE) gene modification in transgenic animals: Functional consequences of selected exon and regulatory region deletion

Another AChE gene targeted mouse strain involving a region in the first intron, found to be critical for AChE expression in muscle cells [S. Camp, L. Zhang, M. Marquez, B. delaTorre, P. Taylor, Knockout mice with deletions of alternatively spliced exons of Acetylcholinesterase, in: N.C. Inestrosa, E.O. Campus (Eds.), VII International Meeting on Cholinesterases, Pucon-Chile Cholinesterases in the Second Millennium: Biomolecular and Pathological Aspects. P. Universidad Catholica de Chile-FONDAP Biomedicina, 2004, pp. 43-48; R.Y.Y. Chan, C. Boudreau-Larivière, L.A. Angus, F. Mankal, B.J. Jasmin, An intronic enhancer containing an N-box motif is required for synapse- and tissue-specific expression of the acetylcholinesterase gene in skeletal muscle fibers. Proc. Natl. Acad. Sci. USA 96 (1999) 4627-4632], is also presented. The intronic region was floxed and then deleted by mating with Ella-cre transgenic mice. The deletion of this region produced a dramatic phenotype; a mouse with near normal AChE expression in brain and other CNS tissues, but no AChE expression in muscle. Phenotype and AChE tissue activities are compared with the total AChE knockout mouse [W. Xie, J.A. Chatonnet, P.J. Wilder, A. Rizzino, R.D. McComb, P. Taylor, S.H. Hinrichs, O. Lockridge, Postnatal developmental delay and supersensitivity to organophosphate in gene-targeted mice lacking acetylcholinesterase. J. Pharmacol. Exp. Ther. 293 (3) (2000) 896-902].