JAX Mouse Strain Datasheet - 005987

129-Ache^tm1Loc/J

Stock No:: 005987 |; ACHE KO

Targeted Mutation

Cryo Recovery

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

View Genetics

Research Applications

Developmental Biology Research
Neurobiology Research
Research Tools
Sensorineural Research

View All Research Applications

Base Price

Starting at:

$2,595.00 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 119-120:289-99. PubMed: 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 ko; AChE-
Gene Symbol and Name	Ache, acetylcholinesterase
Gene Synonym(s)	ACEE; ARACHE; N-ACHE; YT
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 Genotype

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

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

Mammalian Phenotype Terms by Genotype

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

mortality/aging

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

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
- 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

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

mortality/aging

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

prenatal lethality, incomplete penetrance

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

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

nervous system phenotype

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

hearing/vestibular/ear phenotype

delayed ear emergence
- lack of maturation of the ear structure

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

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 119-120:289-99. PubMed: 10421464 MGI: J:56242

Additional - Ache^tm1Loc related

Bernard V; Girard E; Hrabovska A; Camp S; Taylor P; Plaud B; Krejci E. 2011. Distinct localization of collagen Q and PRiMA forms of acetylcholinesterase at the neuromuscular junction. Mol Cell Neurosci 46(1):272-81. PubMed: 20883790 MGI: J:171303
Blondet B; Carpentier G; Ferry A; Chatonnet A; Courty J. 2010. Localization of butyrylcholinesterase at the neuromuscular junction of normal and acetylcholinesterase knockout mice. J Histochem Cytochem 58(12):1075-82. PubMed: 20805581 MGI: J:170221
Bytyqi AH; Lockridge O; Duysen E; Wang Y; Wolfrum U; Layer PG. 2004. Impaired formation of the inner retina in an AChE knockout mouse results in degeneration of all photoreceptors. Eur J Neurosci 20(11):2953-62. PubMed: 15579149 MGI: J:101277
Chatonnet F; Boudinot E; Chatonnet A; Taysse L; Daulon S; Champagnat J; Foutz AS. 2003. Respiratory survival mechanisms in acetylcholinesterase knockout mouse. Eur J Neurosci 18(6):1419-27. PubMed: 14511322 MGI: J:89715
Cousin X; Strahle U; Chatonnet A. 2005. Are there non-catalytic functions of acetylcholinesterases? Lessons from mutant animal models. Bioessays 27(2):189-200. PubMed: 15666354 MGI: J:95975
Dobbertin A; Hrabovska A; Dembele K; Camp S; Taylor P; Krejci E; Bernard V. 2009. Targeting of acetylcholinesterase in neurons in vivo: a dual processing function for the proline-rich membrane anchor subunit and the attachment domain on the catalytic subunit. J Neurosci 29(14):4519-30. PubMed: 19357277 MGI: J:147425
Duysen EG; Li B; Darvesh S; Lockridge O. 2007. Sensitivity of butyrylcholinesterase knockout mice to (--)-huperzine A and donepezil suggests humans with butyrylcholinesterase deficiency may not tolerate these Alzheimer's disease drugs and indicates butyrylcholinesterase function in neurotransmission. Toxicology 233(1-3):60-9. PubMed: 17194517 MGI: J:130048
Duysen EG; Li B; Xie W; Schopfer LM; Anderson RS; Broomfield CA; Lockridge O. 2001. Evidence for nonacetylcholinesterase targets of organophosphorus nerve agent: supersensitivity of acetylcholinesterase knockout mouse to VX lethality J Pharmacol Exp Ther 299(2):528-35. PubMed: 11602663 MGI: J:103438
Duysen EG; Stribley JA; Fry DL; Hinrichs SH; Lockridge O. 2002. Rescue of the acetylcholinesterase knockout mouse by feeding a liquid diet; phenotype of the adult acetylcholinesterase deficient mouse. Brain Res Dev Brain Res 137(1):43-54. PubMed: 12128253 MGI: J:78335
Espallergues J; Galvan L; Sabatier F; Rana-Poussine V; Maurice T; Chatonnet A. 2010. Behavioral phenotyping of heterozygous acetylcholinesterase knockout (AChE+/-) mice showed no memory enhancement but hyposensitivity to amnesic drugs. Behav Brain Res 206(2):263-73. PubMed: 19766675 MGI: J:153967
Hartmann J; Kiewert C; Duysen EG; Lockridge O; Greig NH; Klein J. 2007. Excessive hippocampal acetylcholine levels in acetylcholinesterase-deficient mice are moderated by butyrylcholinesterase activity. J Neurochem 100(5):1421-9. PubMed: 17212694 MGI: J:156049
Li B; Duysen EG; Volpicelli-Daley LA; Levey AI; Lockridge O. 2003. Regulation of muscarinic acetylcholine receptor function in acetylcholinesterase knockout mice. Pharmacol Biochem Behav 74(4):977-86. PubMed: 12667913 MGI: J:102434
Li B; Stribley JA; Ticu A; Xie W; Schopfer LM; Hammond P; Brimijoin S; Hinrichs SH; Lockridge O. 2000. Abundant tissue butyrylcholinesterase and its possible function in the acetylcholinesterase knockout mouse. J Neurochem 75(3):1320-31. PubMed: 10936216 MGI: J:64025
Mesulam MM; Guillozet A; Shaw P; Levey A; Duysen EG; Lockridge O. 2002. Acetylcholinesterase knockouts establish central cholinergic pathways and can use butyrylcholinesterase to hydrolyze acetylcholine. Neuroscience 110(4):627-39. PubMed: 11934471 MGI: J:126281
Mouisel E; Blondet B; Escourrou P; Chatonnet A; Molgo J; Ferry A. 2006. Outcome of acetylcholinesterase deficiency for neuromuscular functioning. Neurosci Res 55(4):389-96. PubMed: 16766072 MGI: J:112809
Silveyra MX; Garcia-Ayllon MS; Serra-Basante C; Mazzoni V; Garcia-Gutierrez MS; Manzanares J; Culvenor JG; Saez-Valero J. 2012. Changes in acetylcholinesterase expression are associated with altered presenilin-1 levels. Neurobiol Aging 33(3):627.e27-37. PubMed: 21621296 MGI: J:188205
Volpicelli-Daley LA; Hrabovska A; Duysen EG; Ferguson SM; Blakely RD; Lockridge O; Levey AI. 2003. Altered striatal function and muscarinic cholinergic receptors in acetylcholinesterase knockout mice Mol Pharmacol 64(6):1309-16. PubMed: 14645660 MGI: J:103439
Xie W; Stribley JA; Chatonnet A; Wilder PJ; Rizzino A; McComb RD; Taylor P; Hinrichs SH; Lockridge O. 2000. Postnatal developmental delay and supersensitivity to organophosphate in gene-targeted mice lacking acetylcholinesterase. J Pharmacol Exp Ther 293(3):896-902. PubMed: 10869390 MGI: J:76453

Pricing & Availability

Cryo Recovery

Domestic
International

Live Mouse

Age

Genotype

Price

weeks

Cryorecovery - Pricing

Service	Genotype	Price
	Heterozygous or Wild-type for Ache<tm1Loc>

We will fulfill your order by providing at least two carriers for each strain ordered. The total number, sex, and genotypes provided will vary, although typically 8 or more animals are provided. Please check genotypes which will be recovered. While the genotypes of all animals produced will be communicated to you prior to scheduling shipment, the genotypes of animals provided may not reflect the mating scheme and genotypes described in the strain description. Animals are typically ready to ship in 11-14 weeks. If a second recovery is required to produce the minimum number of animals, then delivery time would increase to approximately 25 weeks. If we fail to produce animals of the correct genotype, you will not be charged. We cannot guarantee the reproductive success of mice shipped to your facility. If the mice are lost after the first three days (post-arrival) or do not produce progeny at your facility, a new order and fee will be necessary.

Cryorecovery to establish a Dedicated Supply for greater quantities of mice. Mice recovered can be used to establish a dedicated colony to contractually supply you mice according to your requirements. Price by quotation.

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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.

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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 Genotype

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

Mammalian Phenotype Terms by Genotype

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

mortality/aging

homeostasis/metabolism phenotype

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

mortality/aging

growth/size/body region phenotype

behavior/neurological phenotype

nervous system phenotype

hearing/vestibular/ear phenotype

vision/eye phenotype

craniofacial phenotype

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 * 129X1/SvJ

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

Additional - Ache^tm1Loc related