Production of the Butyrylcholinesterase Knockout Mouse

摘要: The butyrylcholinesterase (BChE [EC 3.1.1.8]) knockout mouse is a model for BChE deficiency in humans. existence of genetic variants human was discovered after new muscle relaxant, succinylcholine, introduced into the practice medicine late 1950s. People with atypical variant were unable to breathe 2 h receiving dose intended paralyze 3-5 min (Kalow and Gunn, 1957, 1959). later found have single-amino-acid mutation at Asp-70 (McGuire et al., 1989), which decreased affinity all positively charged compounds. Though mutant one most commonly encountered cases succinylcholine apnea, an additional 58 mutations coding sequence been reported. frequency American population known (Lockridge, 1990). One person out 25 carries allele (D70G), whereas 1 2500 homozygous D70G. frequent mutation, A539T, carried by every 4 form 69 (Bartels 1992). A539T associated 33% decrease plasma activity. Some people no detectable activity plasma, owing that truncates protein, or inactivates it. silent 160 carriers, 110,000 homozygotes. mice are models literature contains documentation health BChE, other than say they healthy. We know nothing about their life expectancy, fertility, risk cognitive impairment, heart disease, susceptibility toxins. will allow us test hypothesis function detoxify poisons role physiological functions.