Description

The genotypes of the animals provided may not reflect those discussed in the strain description or the mating scheme utilized by The Jackson Laboratory prior to cryopreservation. Please inquire for possible genotypes for this specific strain.

Strain Information

Type Coisogenic; Mutant Strain; Targeted Mutation; Additional information on Genetically Engineered and Mutant Mice. Visit our online Nomenclature tutorial. Species laboratory mouse   Donating Investigator Oksana Lockridge,   Eppley Inst. (Univ of Nebraska Med Cntr)

Description
Mice homozygous for this BChE mutant allele are viable and fertile with no reported spontaneous abnormalities. All tissues and plasma from homozygous mice are devoid of BChE activity. As BChE (butyrylcholinesterase) is a bioscavenger molecule protecting acetylcholinesterase (AChE) activity against nerve agents and organophosphates, homozygous BChE-deficiency leads to impaired protection from toxic compounds. These BChE mutant mice are a model for human butyrylcholinesterase deficiency and may be useful for studying metabolic effects of organophosphorus toxicants or nerve agents, neurotransmitter function, and anti-Alzheimer's drug therapies.

Of note, 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
The targeting vector was designed to replace the sequence containing the splice junction between intron 1 and exon 2 through the entire signal peptide (including the translation start site and the first 102 amino acids of the encoded BChE protein) with a neomycin cassette. The construct was electroporated into 129S1/Sv-derived CJ7 embryonic stem (ES) cells. Correctly targeted ES cells were injected into recipient blastocysts. The resulting chimeric animals were crossed to 129S1/SvImJ inbred mice. Mutant mice were backcrossed to 129S1/SvImJ for more than 10 generations prior to arrival at The Jackson Laboratory.

Control Information

	Control
	002448 129S1/SvImJ
Considerations for Choosing Controls

Related Strains

Strains carrying   Bche^tm1Loc allele

008087

B6.129S1-Bchetm1Loc/J

View Strains carrying   Bche^tm1Loc     (1 strain)

Phenotype

Phenotype Information

View Related Disease (OMIM) Terms

Related Disease (OMIM) Terms

Butyrylcholinesterase; BCHE - Models with phenotypic similarity to human disease where etiologies involve orthologs.1

1 Human genes are associated with this disease. Orthologs of those genes appear in the mouse genotype(s).

View Mammalian Phenotype Terms

Mammalian Phenotype Terms

      assigned by genotype

Bche^tm1Loc/Bche⁺

        involves: 129S1/Sv

• life span-post-weaning/aging
• increased sensitivity to xenobiotic induced morbidity/mortality (MGI Ref ID J:130048)
  • donepezil-treated mice die within 24 hours unlike similarly treated controls
  • (-)-huperzin A-treated mice die within 24 hours unlike similarly treated controls
• homeostasis/metabolism phenotype
• increased physiological sensitivity to xenobiotics (MGI Ref ID J:130048)
  • treatment with donepezil induces intermediate symptoms with all mice dying or moribund within 24 hours unlike similarly treated wild-type mice that recover within 24 hours
  • donepezil-treated mice fail to recover normal body temperature unlike similarly treated wild-type mice
  • (-)-huperzin A-treated mice exhibit protosis, salivation, and lacrimation with death occurring within 24 hours of treatment unlike similarly treated mice
• increased sensitivity to xenobiotic induced morbidity/mortality (MGI Ref ID J:130048)
  • donepezil-treated mice die within 24 hours unlike similarly treated controls
  • (-)-huperzin A-treated mice die within 24 hours unlike similarly treated controls

Bche^tm1Loc/Bche^tm1Loc

        involves: 129S1/Sv

• life span-post-weaning/aging
• increased sensitivity to xenobiotic induced morbidity/mortality (MGI Ref ID J:130048)
  • donepezil-treated mice die within 3 hours unlike similarly treated controls
  • (-)-huperzin A-treated mice die within 10 minutes unlike similarly treated controls
• reproductive system phenotype
• *normal* reproductive system phenotype (MGI Ref ID J:124975)
  • mice are fertile
• homeostasis/metabolism phenotype
• increased physiological sensitivity to xenobiotics (MGI Ref ID J:130048)
  • treatment with donepezil induces clonic, jerking convulsions and death within 3 hours unlike similarly treated wild-type mice that recover within 24 hours
  • (-)-huperzin A-treated mice exhibit protosis, salivation, and lacrimation with death occurring within 10 minutes of treatment unlike similarly treated mice
  • however, mice exhibit a normal reaction to CPO and echothiophate
• increased sensitivity to xenobiotic induced morbidity/mortality (MGI Ref ID J:130048)
  • donepezil-treated mice die within 3 hours unlike similarly treated controls
  • (-)-huperzin A-treated mice die within 10 minutes unlike similarly treated controls

View Research Applications

Research Applications

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

Cancer Research
Toxicology

Metabolism Research

Neurobiology Research
Neuromuscular Defects
Neurotransmitter Receptor and Synaptic Vesicle Defects
Receptor Defects
      cholinergic receptor
Tremor Defects

Research Tools
Cancer Research
Metabolism Research
Neurobiology Research
Sensorineural Research
Toxicology Research
      drug metabolism
      drug/compound testing

Bche^tm1Loc related

Neurobiology Research
Alzheimer's Disease

Genes & Alleles

Gene & Allele Information

Allele Symbol		Bchetm1Loc
Allele Name		targeted mutation 1, Oksana Lockridge
Allele Type		Targeted (knock-out)
Common Name(s)		BChE KO; BChE-;
Mutation Made By		Oksana Lockridge,   Eppley Inst. (Univ of Nebraska Med Cntr)
Strain of Origin		129S1/Sv-Oca2<+> Tyr<+> Kitl<+>
ES Cell Line Name		CJ7
ES Cell Line Strain		129S1/Sv-Oca2<+> Tyr<+> Kitl<+>
Gene Symbol and Name		Bche, butyrylcholinesterase
Chromosome		3
Gene Common Name(s)		C730038G20Rik; CHE1; E1; RIKEN cDNA C730038G20 gene;
Molecular Note		891bp of the gene is replaced with a neomycin selection cassette, including 485bp from the 3' end of intron 1 and 406bp from the 5' end of exon 2. The region encoding the entire signal peptide, the translation start site, and the first 102 amino acids ofthe mature protein is deleted. [MGI Ref ID J:124975]

Genotyping

Genotyping Information

Genotyping Protocols

Bche^tm1Loc, Standard PCR

Helpful Links

Genotyping resources and troubleshooting

References

References

Selected Reference(s)

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 Ref ID J:130048]

Li B; Duysen EG; Saunders TL; Lockridge O. 2006. Production of the butyrylcholinesterase knockout mouse. J Mol Neurosci 30(1-2):193-5. [PubMed: 17192674]  [MGI Ref ID J:124975]

Additional References

Bche^tm1Loc related

Duysen EG; Li B; Lockridge O. 2009. The butyrylcholinesterase knockout mouse a research tool in the study of drug sensitivity, bio-distribution, obesity and Alzheimer's disease. Expert Opin Drug Metab Toxicol 5(5):523-8. [PubMed: 19416087]  [MGI Ref ID J:148458]

Health & husbandry

The genotypes of the animals provided may not reflect those discussed in the strain description or the mating scheme utilized by The Jackson Laboratory prior to cryopreservation. Please inquire for possible genotypes for this specific strain.

Health & Colony Maintenance Information

Colony Maintenance

Breeding & Husbandry	When maintaining a live colony, these mice may be bred as heterozygotes or homozygotes.

Purchasing information

Pricing, Supply Level & Notes, Controls, General Terms & Conditions

Pricing

Supply Details

Standard Supply

Cryopreserved. Ready for recovery. Please refer to pricing and supply notes for further information.

Supply Notes

Cryorecovery - Standard. We will fulfill your order by providing at least two pair of mice, at least one animal of each pair carrying the mutation of interest. The total number of animals provided, their gender and genotype will vary. Please inquire if larger numbers of animals with specific genotype and genders are needed. Animals typically ship between 13 and 16 weeks from the date of your order. If a second cryorecovery is needed in order to provide the minimum number of animals, animals will ship within 25 weeks. IMPORTANT NOTE: The genotypes of animals provided may not reflect the mating scheme utilized by The Jackson Laboratory prior to cryopreservation, or that discussed in the strain description. Please inquire about possible genotypes which will be recovered for this specific strain. The Jackson Laboratory 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. For more information on Dedicated Supply, please contact JAX® Services, Tel: 1-800-422-6423 (from U.S.A., Canada or Puerto Rico only) or 1-207-288-5845 (from any location). This strain is included in the Induced Mutant Resource Colony collection.

Control Information

	Control
	002448 129S1/SvImJ
Considerations for Choosing Controls
USA, Canada and Mexico - Control Pricing Information for Genetically Engineered Mutant Strains.
International - Control Pricing Information for Genetically Engineered Mutant Strains.

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Terms are granted by individual review and stated on the customer invoice(s) and account statement. These transactions are payable in U.S. currency within the granted terms. Payment for services, products, shipping containers, and shipping costs that are rendered are expected within the payment terms indicated on the invoice or stated by contract. Invoices and account balances in arrears of stated terms may result in The Jackson Laboratory pursuing collection activities including but not limited to outside agencies and court filings.

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The Jackson Laboratory's Genotype Promise

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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Terms of Use

Terms of Use

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Contact information

General inquiries

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phone:	207-288-6470
fax:	207-288-6655

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