Overview

Also Known As:ACHE KO

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).

Donating Investigator

Dr. Oksana Lockridge, Eppley Inst. (Univ of Nebraska Med Cntr)

Genetic overview

Genetic Background	Generation

Ache^tm1Loc

Allele Type	Gene Symbol	Gene Name
Targeted (Null/Knockout)	Ache	acetylcholinesterase

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Research Applications

Research Tools
Developmental Biology Research
Neurobiology Research
Sensorineural Research

View All Research Applications

Base Price

Starting at:

$2,854.50 Domestic price Cryo Recovery

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Details

Detailed Description

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.

Development

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.

Control Suggestions

Wild-type from the colony

Additional Information

Considerations for Choosing Controls

Selected References

Xie W; Wilder PJ; Stribley J; Chatonnet A; Rizzino A; Taylor P; Hinrichs SH; Lockridge O. 1999. Knockout of one acetylcholinesterase allele in the mouse. Chem Biol Interact 119-120:289-99PubMed: 10421464 MGI: J:56242

View All References

Genetics

Ache^tm1Loc

Allele Symbol: Ache^tm1Loc

Allele Name	targeted mutation 1, Oksana Lockridge
Allele Type	Targeted (Null/Knockout)
Allele Synonym(s)	AChE-; AChE ko
Gene Symbol and Name	Ache, acetylcholinesterase
Gene Synonym(s)
Strain of Origin	(129X1/SvJ x 129S1/Sv)F1-Kitl⁺
Chromosome	5
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.

Disease/Phenotype

Disease Terms

Research Areas By Phenotype

This mouse can be used to support research in many areas including:

Research Tools
- Toxicology Research
  - drug metabolism
  - drug/compound testing
- Sensorineural Research
  - retinal degeneration
Developmental Biology Research
- Perinatal Lethality
  - Homozygous
- Embryonic Lethality (Homozygous)
  - incomplete
- Neurodevelopmental Defects
Neurobiology Research
- Alzheimer's Disease
- Parkinson's Disease
- Neurodevelopmental Defects
- Neurotransmitter Receptor and Synaptic Vesicle Defects
- Tremor Defects
Sensorineural Research
- Retinal Degeneration

Mammalian Phenotype Terms by Genotype

The following phenotype relates to a compound genotype created using this strain

Genotype: Ache^tm1Loc/Ache^tm1Loc
involves: 129S1/Sv * 129S6/SvEvTac * 129X1/SvJ

behavior/neurological phenotype

abnormal gait
- null mice are born at frequency of 20% instead of expected 25%

abnormal posture
- splayed feet and legs

circling
- null mice exhibit continuous circling movement upon separation from the nest

impaired righting response
- no righting reflex develops even by 21 days of age, whereas wild-type controls show reflex by 8 days of age

tremors
- fine motor tremor observed at 3-4 days of age

mortality/aging

postnatal lethality, complete penetrance
- pups die during the postnatal period between P13-21; none survive beyond 21 days

prenatal lethality, incomplete penetrance

nervous system phenotype

abnormal cerebral hemisphere morphology
- cerebral hemispheres are transulucent in 12-day old mice, whereas they are opaque in wild-type littermates

vision/eye phenotype

eyelids fail to open
- failure of eyelids to open; sealed even on P21, while littermates open on P8 to 12

craniofacial phenotype

delayed ear emergence
- lack of maturation of the ear structure

growth/size/body region phenotype

decreased body weight
- weight is lower than wild-type from P2 onward, with a clear difference noted at 7 days after birth; weights decreased 1-2 days prior to death at ~P14

delayed ear emergence
- lack of maturation of the ear structure

hearing/vestibular/ear phenotype

delayed ear emergence
- lack of maturation of the ear structure

Genotype: Ache^tm1Loc/Ache^tm1Loc
involves: 129S1/Sv * 129X1/SvJ

homeostasis/metabolism phenotype

abnormal physiological response to xenobiotic
- donepezil-treated mice exhibit a thick exudates forming over the eyes unlike similarly treated wild-type mice but similar to homozygous mice under stress
- Normal - however, donepezil-treated mice do not exhibit a change in body temperature

increased physiological sensitivity to xenobiotic
- CPO-treated mice exhibit cholinergic symptoms and die within 11 minutes unlike simialrly treated wild-type mice

increased sensitivity to xenobiotic induced morbidity/mortality
- CPO-treated mice die within 11 minutes unlike simiarly treated wild-type mice

mortality/aging

increased sensitivity to xenobiotic induced morbidity/mortality
- CPO-treated mice die within 11 minutes unlike simiarly treated wild-type mice

References

Xie W; Wilder PJ; Stribley J; Chatonnet A; Rizzino A; Taylor P; Hinrichs SH; Lockridge O. 1999. Knockout of one acetylcholinesterase allele in the mouse. Chem Biol Interact 119-120:289-99PubMed: 10421464 MGI: J:56242

Additional - Ache^tm1Loc related

Technical Support

CONTACT TECHNICAL SUPPORT

Genotyping Protocols
- Standard PCR:Ache
- Genotyping resources and troubleshooting
Breeding Considerations

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.
- Additional Breeding and Husbandry Support
Citation
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.

Animal Health Reports

Facility Barrier Level Descriptions

Production of mice from cryopreserved embryos or sperm occurs in a maximum barrier room, G200

Pricing & Availability

Cryo Recovery

Domestic
International

Live Mouse

Age

Genotype

Price

weeks

Cryorecovery - Pricing

Service/Product	Description	Price
	Heterozygous or Wild-type for Ache<tm1Loc>

Payment Terms and Conditions

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The Jackson Laboratory has rigorous genetic quality control and mutant gene genotyping programs to ensure the genetic background of JAX® Mice strains as well as the genotypes of strains with identified molecular mutations. JAX® Mice strains are only made available to researchers after meeting our standards. However, the phenotype of each strain may not be fully characterized and/or captured in the strain data sheets. Therefore, we cannot guarantee a strain's phenotype will meet all expectations. To ensure that JAX® Mice will meet the needs of individual research projects or when requesting a strain that is new to your research, we suggest ordering and performing tests on a small number of mice to determine suitability for your particular project. We do not guarantee breeding performance and therefore suggest that investigators order more than one breeding pair to avoid delays in their research.

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General Terms and Conditions

Questions about Terms of Use

Licensing Information

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Also Known As:ACHE KO

Donating Investigator

Genetic overview

Research Applications

Base Price

Detailed Description

Development

Control Suggestions

Additional Information

Selected References

Achetm1Loc

Allele Symbol: Achetm1Loc

Disease Terms

Research Areas By Phenotype

This mouse can be used to support research in many areas including:

Mammalian Phenotype Terms by Genotype

Genotype: Achetm1Loc/Achetm1Locinvolves: 129S1/Sv * 129S6/SvEvTac * 129X1/SvJ

behavior/neurological phenotype

mortality/aging

nervous system phenotype

vision/eye phenotype

craniofacial phenotype

growth/size/body region phenotype

hearing/vestibular/ear phenotype

Genotype: Achetm1Loc/Achetm1Locinvolves: 129S1/Sv * 129X1/SvJ

homeostasis/metabolism phenotype

mortality/aging

References

Additional - Achetm1Loc related

Genotyping Protocols

Breeding Considerations

Citation

Animal Health Reports

Production of mice from cryopreserved embryos or sperm occurs in a maximum barrier room, G200

Live Mouse

Cryorecovery - Pricing

Payment Terms and Conditions

The Jackson Laboratory's Genotype Promise

Terms Of Use

Licensing Information

JAX® Mice, Products & Services Conditions of Use

No Warranty

Credit for PRODUCTS or SERVICES

Animal Care and Use for SERVICES

No Liability

Ache^tm1Loc

Allele Symbol: Ache^tm1Loc

Genotype: Ache^tm1Loc/Ache^tm1Loc
involves: 129S1/Sv * 129S6/SvEvTac * 129X1/SvJ

Genotype: Ache^tm1Loc/Ache^tm1Loc
involves: 129S1/Sv * 129X1/SvJ

Additional - Ache^tm1Loc related