Description

Strain Information

Type Congenic; Mutant Strain; Targeted Mutation; Additional information on Genetically Engineered and Mutant Mice. Visit our online Nomenclature tutorial. Additional information on Congenic nomenclature. Mating System See Colony Maintenance Species laboratory mouse Generation N11+F2 (23-OCT-08)   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.

In an attempt to offer alleles on well-characterized or multiple genetic backgrounds, alleles are frequently moved to a genetic background different from that on which an allele was first characterized. As the BChE mutation was originally described on a 129S1/Sv genetic background (129S1-BChE mice), it should be noted that the phenotype of B6-BChE mice could vary from that originally described. We will modify the strain description if necessary as published results become available.

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. Heterozygous mutant mice were then backcrossed to C57BL/6 for more than 10 generations prior to arrival at The Jackson Laboratory.

Control Information

	Control
	000664 C57BL/6J
Considerations for Choosing Controls

Related Strains

Strains carrying   Bche^tm1Loc allele

008077

129S1/Sv-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

The following phenotype information may relate to a genetic background differing from this JAX^® Mice strain.

Bche^tm1Loc/Bche⁺

        involves: 129S1/Sv

• life span-post-weaning/aging
• abnormal induced morbidity/mortality (MGI Ref ID J:130048)
  • donepezil-treated mice die within 24 hours unlike similarly treated mice
  • (-)-huperzin A-treated mice die within 24 hours unlike similarly treated mice
• homeostasis/metabolism phenotype
• increased 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

Bche^tm1Loc/Bche^tm1Loc

        involves: 129S1/Sv

• life span-post-weaning/aging
• abnormal induced morbidity/mortality (MGI Ref ID J:130048)
  • donepezil-treated mice die within 3 hours unlike similarly treated mice
  • (-)-huperzin A-treated mice die within 10 minutes unlike similarly treated mice
• reproductive system phenotype
• *normal* reproductive system phenotype (MGI Ref ID J:124975)
  • mice are fertile
• homeostasis/metabolism phenotype
• increased 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

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, STD PCR, vers. 1

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

Health & Colony Maintenance Information

Animal Health Reports

Room Number           AX11

Colony Maintenance

Breeding & Husbandry	When maintaining a live colony, these mice may be bred as homozygotes.
Mating System	See above
Diet Information	LabDiet® 5K52/5K67

Purchasing information

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

Pricing

Supply Details

Standard Supply

Repository-Live. A collection of over 1000 strains maintained as live colonies. Individual colonies are sized to meet current customer demand. Delivery for orders of 10 mice or less ranges on average from one to eight weeks; mice are generally shipped between four to six weeks of age with a maximum shipping age of approximately nine weeks. Colony sizes do not generally support stringent age specifications for large volumes of mice; however custom orders and larger quantities of mice are easily arranged. Estimated ship dates for all orders provided within two business days following order placement.

Supply Notes

Usually shipped between four and eight weeks of age. This strain is included in the Induced Mutant Resource Colony collection.

Control Information

	Control
	000664 C57BL/6J
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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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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