These mutant mice lack exon 5 of the Ces1c gene, abolishing gene function. These mice may be useful as a model in which to measure and protect against nerve agents and for testing drugs that are hydrolyzed by ES1.
Dr. Oksana Lockridge, Eppley Inst. (Univ of Nebraska Med Cntr)
Genetic Background | Generation |
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N2F11+pN1F10
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Allele Type | Gene Symbol | Gene Name |
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Targeted (Null/Knockout) | Ces1c | carboxylesterase 1C |
These Es1-/- knockout mice lack exon 5 of the carboxylesterase 1C (Ces1c or Es1) gene, abolishing gene function. Mice that are homozygous for this allele are viable, fertile, and normal in size. Carboxylesterases are expressed in the liver and are found in many tissues including the intestine, lung, and in the plasma of mice, but not in the plasma of humans. To mimic the lack of ES1 in human plasma and the resulting increase in susceptibility to nerve agents and to drugs that are hydrolyzed by ES1, these mice have had plasma ES1 activity eliminated. ES1 acts as an organophosphorus (OP) bioscavenger which reduces the level of OP reaching biologically relevant targets and protects against lethal toxicity from nerve agents. Es1-/- mice have normal acetylcholinesterase (AChE), butyrylcholinesterase (BChE), and paraoxonase plasma activity, with normal levels of carboxylesterase activity in other tissues, including the brain, lungs, liver, intestines, and heart. These mutant mice react in a similar manner as control mice to some low toxicity OP agents, such as cyclosarin thiocholine analog and tabun, and are protected against some nerve agents, such as chlorpyrifos and chlorpyrifos oxon. They also display increased sensitivity to soman coumarin as noted by decreased body temperature and increased morbidity. These mice may be useful as a model in which to measure and protect against nerve agents and for testing drugs that are hydrolyzed by ES1.
A targeting vector was designed to insert a loxP site upstream of exon 5, and a neomycin resistance (neo) cassette followed by a single loxP site downstream of exon 5 of the carboxylesterase 1C (Ces1c or Es1) gene. The construct was electroporated into C57BL/6-derived Bruce 4 embryonic stem (ES) cells. Correctly targeted ES cells were injected into blastocysts and resulting chimeric mice were bred to C57BL/6 mice. These mice were then bred to cre-deleter mice on a C57BL/6 background to remove exon 5 and the neo cassette. Subsequently these mice were bred to C57BL/6J for at least 2 generations to generate a colony of Es1-/- mice. Upon arrival at The Jackson Laboratory, mice were bred to C57BL/6J inbred mice (Stock No. 000664) for at least one generation to establish the colony.
Allele Name | targeted mutation 1.1, Oksana Lockridge |
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Allele Type | Targeted (Null/Knockout) |
Allele Synonym(s) | |
Gene Symbol and Name | Ces1c, carboxylesterase 1C |
Gene Synonym(s) | |
Strain of Origin | B6.Cg-Thy1a |
Chromosome | 8 |
Molecular Note | A targeting vector was designed to insert a loxP site upstream of exon 5, and a neomycin resistance (neo) cassette followed by a single loxP site downstream of exon 5. Cre-mediated recombination removed exon 5 and the neo cassette. This deletion is predicted to abolish protein function. The absence of carboxylesterase activity in the plasma was confirmed by enzymatic assay. |
Mutations Made By | Dr. Oksana Lockridge, Eppley Inst. (Univ of Nebraska Med Cntr) |
When maintaining a live colony, homozygous mice may be bred together.
When using the B6(Cg)-Ces1ctm1.1Loc/J mouse strain in a publication, please cite the originating article(s) and include JAX stock #014096 in your Materials and Methods section.
Service/Product | Description | Price |
---|---|---|
Heterozygous for Ces1c<tm1.1Loc> |
Frozen Mouse Embryo | B6(Cg)-Ces1c<tm1.1Loc>/J Frozen Embryo | $2595.00 |
Frozen Mouse Embryo | B6(Cg)-Ces1c<tm1.1Loc>/J Frozen Embryo | $2595.00 |
Frozen Mouse Embryo | B6(Cg)-Ces1c<tm1.1Loc>/J Frozen Embryo | $3373.50 |
Frozen Mouse Embryo | B6(Cg)-Ces1c<tm1.1Loc>/J Frozen Embryo | $3373.50 |
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