title: Production of the butyrylcholinesterase knockout mouse.
abstract: The butyrylcholinesterase (BChE [EC 3.1.1.8]) knockout mouse is a model for BChE deficiency in humans. The existence of genetic variants of human BChE was discovered after a new muscle relaxant, succinylcholine, was introduced into the practice of medicine in the late 1950s. People with the atypical variant were unable to breathe for 2 h after receiving a dose intended to paralyze for 3-5 min (Kalow and Gunn, 1957, 1959). The atypical variant was later found to have a single-amino-acid mutation at Asp-70 (McGuire et al., 1989), which decreased the affinity of BChE for all positively charged compounds. Though the atypical BChE mutant is the one most commonly encountered in cases of succinylcholine apnea, an additional 58 mutations in the BChE coding sequence have been reported. The frequency of BChE mutations in the American population is known (Lockridge, 1990). One person out of 25 carries one atypical allele (D70G), whereas 1 out of 2500 is homozygous for D70G. The most frequent mutation, A539T, is carried by 1 person out of every 4 and is found in homozygous form in 1 person out of 69 (Bartels et al., 1992). The homozygous A539T form is associated with a 33% decrease in plasma BChE activity. Some people have no detectable BChE activity in plasma, owing to a mutation that truncates the protein, or inactivates it. The frequency of silent BChE is 1 out of 160 for carriers, and 1 out of 110,000 for homozygotes. The BChE knockout mice are models for silent BChE in humans. The literature contains no documentation of the health of people with silent BChE, other than to say they are healthy. We know nothing about their life expectancy, fertility, risk of cognitive impairment, risk of heart disease, or susceptibility to toxins. The BChE knockout mouse will allow us to test the hypothesis that the function of BChE is to detoxify poisons and will allow us to test the role of BChE in other physiological functions.
authors.affiliation: University of Nebraska Medical Center, Eppley Institute, Omaha, NE 68198-6805, USA.
authors.forename: Bin
authors.initials: B
authors.lastname: Li
authors.forename: Ellen G
authors.initials: EG
authors.lastname: Duysen
authors.forename: Thomas L
authors.initials: TL
authors.lastname: Saunders
authors.forename: Oksana
authors.initials: O
authors.lastname: Lockridge
mesh_terms: D017398:Alternative Splicing; D000818:Animals; D002091:Butyrylcholinesterase / Q000172:deficiency* / Q000235:genetics*; D005091:Exons; D005822:Genetic Vectors; D015698:Genomic Library; D008658:Inactivation, Metabolic; D007438:Introns; D051379:Mice; D018345:Mice, Knockout
chemical_list: D002091:Butyrylcholinesterase