Updated 5 January 2009
Transgene: A targeting vector was designed to replace exons 2-5 of the endogenous
gene with a neomycin resistance gene. The construct was electroporated into (129X1/SvJ
x 129S1/Sv)F1-derived R1 embryonic stem (ES) cells. Correctly targeted ES cells
(line 3D6) were injected into C57BL/6 blastocysts. The resulting chimeric males
were bred to 129S6/SvEvTac females.
Mutation: Targeted mutation 1
Breeding: Heterozygous pups were bred to 129S6/SvEvTac for more than 10 generations
before arrival at The Jackson Laboratory.
TJL mating system: heterozygote x +/+ sibling (female x male). Homozygous mice do
not reproduce. A high fat diet is necessary for gestation of homozygous pups from
Het x wt matings.
Mouse strain: 129-Achetm1Loc
Deletion of four exons of the AChE gene reduced AChE activity by half in het-mutant
mice and totally eliminated AChE activity in null animals.
Normal neuromuscular junction of 12-day-old null animals.
Respiratory motor-neurons are protected from the tonic activity induced by cholinergic
Homozygous mice have drastic reduction of the M1, M2, and M4 muscarinic acetylcholine
receptors in the cortex and hippocampus with decreased cell surface localization
and increased intracellular localization of these receptors.
Homozygous mice have defective formation of the inner retina associated with apoptotic
photoreceptor degeneration with age.
Homozygous mice have 25% fetal mortality. Those born have retarded growth, fine
motor tremors, unusual posture and gait, no righting reflex, malformed pinna, and
sealed eyelids. These mice die emaciated and dehydrated by 3 weeks of age (day 21).
Homozygous mice are hypersensitive to organophosphates and bambuterol. Symptoms
of organophosphate poisoning include pulsating paws, body tremor, abnormal gait,
pinpoint pupils, muscle weakness, and early death following seizure. When restrained,
a white mucus forms on the eyes and seizures may occur.
Mice also have several developmental delays, low body mass, decreased pain response,
sexual dysfunction, an inability to chew solid food, and a lack of aggression.
Null mice develop fine motor tremor at day 3 or 4 leading to gait abnormalities
and erratic motion (continuous circling).
Heterozygous mice are viable and fertile with normal maturation and development.
They exhibit intermediate sensitivity to organophosphates and are unaffected by
Contact: The Jackson
Lab, cryopreserved, stock #005987.
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Bytyqi AH, Lockridge O, Duysen E, Wang Y, Wolfrum U, Layer PG. Impaired formation
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Li B, Stribley JA, Ticu A, Xie W, Schopfer LM, Hammond P, Brimijoin S, Hinrichs
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