These Ache knock-out mice exhibit retarded growth, fine motor tremors, unusual posture and gait, no righting reflex, malformed pinna, and sealed eyelids.. They are suitable for studies of toxicology, neuromuscular junctions, nervous system function, neuropsychiatric diseases (Alzheimer's and Parkinson's), and blinding diseases (Retinitis pigmentosa and age-related macular degeneration).
Dr. Oksana Lockridge, Eppley Inst. (Univ of Nebraska Med Cntr)
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. Enriched diets for the nursing female and pups allow homozygous mice to survive to adulthood. Males exhibit no breeding behavior. Homozygous females can become pregnant when bred to heterozygous or wildtype males, but both female and pups do not survive. Acetylcholinesterase (AChE) activity is completely abrogated in serum and tissue from homozygous mice, and approximately half in heterozygotes. Many symptoms of organophosphate poisoning are observed in homozygous mice, including 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. Homozygous mice are hypersensitive to organophosphates and bambuterol. Respiratory motorneurons are protected from the tonic activity induced by cholinergic agonists. Similarly, 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. Heterozygous mice are viable and fertile with normal maturation and development. They exhibit intermediate sensitivity to organophosphates and are unaffected by bambuterol. This mouse may be useful in studies of toxicology, neuromuscular junctions, nervous system function, neuropsychiatric diseases (Alzheimer's and Parkinson's), and blinding diseases (Retinitis pigmentosa and age-related macular degeneration).
The donating investigator has multiple strains available that may be useful for testing toxic compounds, including the AChE-deficient (Stock No. 005987), G117H BChE transgenic (Stock No. 007577), and BChE-deficient (see Stock No. 008077 and Stock No. 008087) mice.
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. Heterozygous pups were bred to 129S6/SvEvTac for more than 10 generations before arrival at The Jackson Laboratory.
|Allele Name||targeted mutation 1, Oksana Lockridge|
|Allele Type||Targeted (Null/Knockout)|
|Allele Synonym(s)||AChE-; AChE ko|
|Gene Symbol and Name||Ache, acetylcholinesterase|
|Strain of Origin||(129X1/SvJ x 129S1/Sv)F1-Kitl+|
|Molecular Note||A 5 kb genomic fragment containing exons 2-5 was replaced by a neomycin resistance gene cassette. Enzymatic activity assays on blood serum derived from homozygous mice confirmed that no functional protein was made from this allele.|
When maintaining a live colony, heterozygous mice are bred with wild type siblings. Homozygous mice do not produce litters. If adult homozygous mice are to be generated, the donating investigator recommends that heterozygous dams are given a high fat diet while gestating and nursing. Homozygous mice should be weaned at day 15 and given a nutrient rich liquid diet. Incisor trimming may be needed for liquid fed mice (Ensure from Abbott Labs). Homozygous mice have improper urination and defecation habits in the nest.
When using the ACHE KO mouse strain in a publication, please cite the originating article(s) and include JAX stock #005987 in your Materials and Methods section.
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