Knockout of one acetylcholinesterase allele in the mouse

Xie, Weihua; Wilder, Phillip J.; Stribley, Judith A.; Chatonnet, Arnaud; Rizzino, Angie; Taylor, Palmer; Hinrichs, Steven H.; Lockridge, Oksana

doi:10.1016/s0009-2797(99)00039-3

Cited by 47 publications

(39 citation statements)

References 17 publications

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“…However, in the mouse, neither collagenic tail gene inactivation (58), which prevented accumulation of all AChE at the synapse, nor ache gene inactivation (59) prevented embryonic development. In these mutant animals, showing delayed postnatal growth, BChE or other carboxylesterases may supply AChE function (58,59). In Drosophila, which has no other cholinesterase than AChE, a mutation in AChE induced abnormal neuronal development (60).…”

Section: Discussionmentioning

confidence: 99%

Zebrafish Acetylcholinesterase Is Encoded by a Single Gene Localized on Linkage Group 7

Bertrand¹,

Chatonnet²,

Takke³

et al. 2001

Journal of Biological Chemistry

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We cloned and sequenced the acetylcholinesterase gene and cDNA of zebrafish, Danio rerio. We found a single gene (ache) located on linkage group LG7. The relative organization of ache, eng2, and shh genes is conserved between zebrafish and mammals and defines a synteny. Restriction fragment length polymorphism analysis was allowed to identify several allelic variations. We also identified two transposable elements in non-coding regions of the gene. Compared with other vertebrate acetylcholinesterase genes, ache gene contains no alternative splicing at 5 or 3 ends where only a T exon is present. The translated sequence is 60 -80% identical to acetylcholinesterases of the vertebrates and exhibits an extra loop specific to teleosts. Analysis of molecular forms showed a transition, at the time of hatching, from the globular G4 form to asymmetric A12 form that becomes prominent in adults. In situ hybridization and enzymatic activity detection on whole embryos confirmed early expression of the acetylcholinesterase gene in nervous and muscular tissues. We found no butyrylcholinesterase gene or activity in Danio. These findings make zebrafish a promising model to study function of acetylcholinesterase during development and regulation of molecular forms assembly in vivo.

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Section: Discussionmentioning

confidence: 99%

Zebrafish Acetylcholinesterase Is Encoded by a Single Gene Localized on Linkage Group 7

Bertrand¹,

Chatonnet²,

Takke³

et al. 2001

Journal of Biological Chemistry

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“…3 , 4 The lack of frequency-dependent inhibiIn AChE+/+ muscle, 0.1 AM d-TC coapplied with tion by BW 284C51 in AChE-/-muscle is consistent 1 /AM BW 284C51 partially antagonized the marked with an absence of the target enzyme in the knocktetanic fade observed in the presence of BW 284C51 out mice. 13,36 alone (Fig. 3A).…”

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confidence: 91%

“…36 Stim ulation of the phrenic nerve in isost u e sU i n C y, alf r a) lated diaphragm preparations from AChE-'-mice revealed large single twitches and sustained tetanic ChE Assays. The AChE and BChE were extracted tensions at 70 and 100 Hz.…”

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confidence: 98%

Reduced acetylcholine receptor density, morphological remodeling, and butyrylcholinesterase activity can sustain muscle function in acetylcholinesterase knockout mice

Adler¹,

Manley²,

Purcell³

et al. 2004

Muscle and Nerve

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“…AChE knockout mice were produced by homologous recombination [34,35]. Exons 2, 3, 4, and 5 of the ACHE gene were deleted, making it impossible to produce an AChE protein.…”

Section: Micementioning

confidence: 99%

Biochemical Markers for Exposure to Low Doses of Organophosphorus Insecticides

Lockridge¹

2003

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Public reporting burden for this collection of information is estimated to average 1 hour per response, including the time for reviewing instructions, searching existing data sources, gathering and maintaining the data needed, and completing and reviewing this collection of information. Send comments regarding this burden estimate or any other aspect of this collection of information, including suggestions for reducing this burden to Washington Headquarters Services, Directorate for Information Operations and Reports, 1215 Jefferson Davis Highway, Suite 1204, Arlington, VA 22202-4302, and to the Office of Management and Budget, Paperwork Reduction Project (0704-0188), Washington, DC 20503 AGENCY USE ONLY (Leave blank)2. REPORT DATE August 2 0 02 REPORT TYPE AND DATES COVEREDAnnual (1 Aug 01 -31 Jul 02) TITLE AND SUBTITLE Biochemical Markers for Exposure to Low Doses of Organophosphorus Insecticides AUTHOR(S)Oksana Lockridge, Ph.D. FUNDING NUMBERS DAMD17-01-1-0776 PERFORMING ORGANIZATION NAME(S) AND ADDRESS(ES)University of Nebraska Medical Center Omaha, Nebraska 68198-6810 E-Mail: olockrid@unmc.edu Though acetylcholinesterase is the primary target of organophosphorus toxicants, our finding that acetylcholinesterase knockout mice are supersensitive to the lethal effects of VX, DFP, chlorpyrifos oxon, and iso-OMPA demonstrates that other important targets exist. The goal of this work is to identify non-acetylcholinesterase targets of organophosphorus toxicants. PERFORMING ORGANIZATION REPORT NUMBER SPONSORING / MONITORING AGENCY NAME(S) AND ADDRESS(ES)UBiotinylated-organophosphate was used to label proteins in mouse brain.The labeled proteins were separated by polyacrylamide gel electrophoresis and visualized with avidin conjugated to a fluorophore.This method has yielded 29 organophosphorus-reactive protein bands in mouse brain.They range in size from 15 to 100 kDa.Rate constants for reaction with biotinylated organophosphate were measured for the 29 proteins as well as for purified human acetylcholinesterase and human butyrylcholinesterase.A method has been developed to screen proteins for reactivity with organophosphorus agents.This work is expected to identify new biological markers for low dose exposure to organophosphorus toxicants and to explain the neurologic symptoms of some of our Gulf War veterans. Introduction. The purpose of this work is to identify proteins that react with low doses of organophosphorus agents (OP). There is overwhelming evidence that acute toxicity of OP is due to inhibition of AChE. However, we have found that the AChE knockout mouse, which has zero AChE, is supersensitive to low doses of OP. The AChE -/-mouse dies at doses of OP that are not lethal to wild-type mice (Duysen et al., 2001;Duysen et al., 2002). This demonstrates that non-AChE targets are involved in OP toxicity. Our goal is to identify new biological markers of exposure to organophosphorus agents. Our strategy uses biotinylated OP to label proteins, which are then visualized with avidin conjugated to a fluorophore....

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Knockout of one acetylcholinesterase allele in the mouse

Cited by 47 publications

References 17 publications

Zebrafish Acetylcholinesterase Is Encoded by a Single Gene Localized on Linkage Group 7

Zebrafish Acetylcholinesterase Is Encoded by a Single Gene Localized on Linkage Group 7

Reduced acetylcholine receptor density, morphological remodeling, and butyrylcholinesterase activity can sustain muscle function in acetylcholinesterase knockout mice

Biochemical Markers for Exposure to Low Doses of Organophosphorus Insecticides

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