Overview

This KEPI KO mutant mouse strain may be useful in studies of morphine analgesia and tolerance.

Donating Investigator

George R. Uhl, NIDA-IRP/NIH

Genetic overview

Genetic Background	Generation

Ppp1r14c^tm1Uhl

Allele Type	Gene Symbol	Gene Name
Targeted (Null/Knockout)	Ppp1r14c	protein phosphatase 1, regulatory inhibitor subunit 14C

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Research Applications

Neurobiology Research
Sensorineural Research

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Base Price

Starting at:

$2,854.50 Domestic price Cryo Recovery

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Details

Detailed Description

Mice that are homozygous for the targeted mutation are viable, fertile, normal in size and do not display any gross physical or behavioral abnormalities. The Donating Investigator reports that the expected number of homozygotes are produced in heterozygous crosses. No gene product (mRNA) is detected by RT-PCR analysis of brain tissue from homozygotes. SNP analysis revealed that the Oprm1 allele variant, which is located close to the targeted gene, is from C57BL/6. Homozygotes exhibit increased phosphatase 1 activity in the thalamus. Homozygotes develop faster morphine tolerance in a hot plate assay ("supraspinal" nociceptive response assessment) and a rightward shift in dose response curve for morphine reward in conditioned place preference when compared to wildtype controls.

Development

A neo cassette-containing targeting vector was used to disrupt exon 1, which contains the initiation codon and the potential PP1 docking motif. The construct was electroporated into 126S6/SvEvTac derived MC1 embryonic stem (ES) cells. Correctly targeted ES cells were injected into C57BL/6J blastocysts. The resulting heterozygous chimeric animals were intercrossed to generate homozygotes. SNP analysis revealed that the Oprm1 allele variant, which is located close to the targeted gene, is from C57BL/6. Upon arrival at The Jackson Laboratory, the mice were crossed to C57BL/6J (Stock No. 000664) at least once to establish the colony.

Selected References

Drgonova J; Zimonjic DB; Hall FS; Uhl GR. 2010. Effect of KEPI (Ppp1r14c) deletion on morphine analgesia and tolerance in mice of different genetic backgrounds: when a knockout is near a relevant quantitative trait locus. Neuroscience 165(3):882-95PubMed: 19819304 MGI: J:159561

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Genetics

Ppp1r14c^tm1Uhl

Allele Symbol: Ppp1r14c^tm1Uhl

Allele Name	targeted mutation 1, George R Uhl
Allele Type	Targeted (Null/Knockout)
Allele Synonym(s)
Gene Symbol and Name	Ppp1r14c, protein phosphatase 1, regulatory inhibitor subunit 14C
Gene Synonym(s)
Strain of Origin	129S6/SvEvTac
Chromosome	10
General Note	The original line on a mixed 129S6/SvEvTac and C57BL/6 background was discontinued in favor of a recombinant line containing regions adjacent to the targeted allele from C57BL/6 (J:159561).
Molecular Note	Exon 1 was replaced with a neo cassette. RT-PCR confirmed the absence of transcript expression.
Mutations Made By	George Uhl, NIDA-IRP/NIH

Disease/Phenotype

Disease Terms

Models with phenotypic similarity to human diseases where etiology is unknown or involving genes where ortholog is unknown.

Research Areas By Phenotype

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

Neurobiology Research
- Behavioral and Learning Defects
Sensorineural Research
- Nociception

Mammalian Phenotype Terms by Genotype

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

Genotype: Ppp1r14c^tm1Uhl/Ppp1r14c^tm1Uhl
involves: 129S6/SvEvTac * C57BL/6J

behavior/neurological phenotype

abnormal behavioral response to addictive substance
- mice the Oprm1 allele from C57BL/6
- following naloxone-precipitated morphine withdrawal, female mice on the original line with the Oprm1 allele from 129S6/SvEvTac exhibit less jumping than males unlike wild-type or recombinant mice the Oprm1 allele from C57BL/6

abnormal conditioned place preference behavior
- Normal - however, locomotion in response to increasing morphine dose in recombinant mice with the Oprm1 allele from C57BL/6 is normal
- recombinant mice with the Oprm1 allele from C57BL/6 exhibit a rightward shift in the dose-response curve for morphine conditioned place preference compared with wild-type mice

enhanced behavioral response to morphine
- Normal - however, a recombinant line with the Oprm1 allele from C57BL/6 exhibit normal analgesic response to morphine
- Normal - however, locomotion in response to increasing morphine dose in recombinant mice with the Oprm1 allele from C57BL/6 is normal
- in a hot plate assay, recombinant mice with an Oprm1 allele from C57BL/6 exhibit faster development of morphine tolerance compared with wild-type mice
- mice with an Oprm1 allele from 129S6/SvEv exhibit increased sensitivity to morphine analgesia in a tail flick or hot plate test compared with wild-type mice which carried the Oprm1 allele from C57BL/6
- om C57BL/6
- recombinant mice with the Oprm1 allele from C57BL/6 exhibit a rightward shift in the dose-response curve for morphine conditioned place preference compared with wild-type mice

increased chemically-elicited antinociception
- Normal - however, a recombinant line with the mutant allele and the Oprm1 allele from C57BL/6 exhibit normal analgesic response to morphine
- mice with an Oprm1 allele from 129S6/SvEv exhibit increased sensitivity to morphine analgesia in a tail flick or hot plate test compared with wild-type mice which carried the Oprm1 allele from C57BL/6
- om C57BL/6

integument phenotype

increased chemically-elicited antinociception
- Normal - however, a recombinant line with the mutant allele and the Oprm1 allele from C57BL/6 exhibit normal analgesic response to morphine
- mice with an Oprm1 allele from 129S6/SvEv exhibit increased sensitivity to morphine analgesia in a tail flick or hot plate test compared with wild-type mice which carried the Oprm1 allele from C57BL/6
- om C57BL/6

mammalian phenotype

behavior/neurological phenotype
- Normal - mice exhibit normal general learning and motor function

mortality/aging

prenatal lethality, incomplete penetrance
- fewer than expected mice are born

Genotype: Ppp1r14c^tm1Uhl/Ppp1r14c⁺
involves: 129S6/SvEvTac * C57BL/6J

behavior/neurological phenotype

abnormal conditioned place preference behavior
- Normal - however, locomotion in response to increasing morphine dose in recombinant mice with the Oprm1 allele from C57BL/6 is normal
- omozygous mice
- recombinant mice with the Oprm1 allele from C57BL/6 exhibit an intermediate rightward shift in the dose-response curve for morphine conditioned place preference compared with wild-type and homozygous mice

enhanced behavioral response to morphine
- Normal - however, locomotion in response to increasing morphine dose in recombinant mice with the Oprm1 allele from C57BL/6 is normal
- omozygous mice
- recombinant mice with the Oprm1 allele from C57BL/6 exhibit an intermediate rightward shift in the dose-response curve for morphine conditioned place preference compared with wild-type and homozygous mice

Genotype: Ppp1r14c^tm1Uhl/Ppp1r14c^tm1Uhl
B6;129S6-Ppp1r14c/J

immune system phenotype

increased susceptibility to Coronaviridae infection
- mice infected with the mouse-adapted SARS-CoV MA15 exhibit more weight loss than wild-type mice and a moderate, but insignificant, increase in viral titers

References

Drgonova J; Zimonjic DB; Hall FS; Uhl GR. 2010. Effect of KEPI (Ppp1r14c) deletion on morphine analgesia and tolerance in mice of different genetic backgrounds: when a knockout is near a relevant quantitative trait locus. Neuroscience 165(3):882-95PubMed: 19819304 MGI: J:159561

Additional References

McDermott JE; Mitchell HD; Gralinski LE; Eisfeld AJ; Josset L; Bankhead A 3rd; Neumann G; Tilton SC; Schafer A; Li C; Fan S; McWeeney S; Baric RS; Katze MG; Waters KM. 2016. The effect of inhibition of PP1 and TNFalpha signaling on pathogenesis of SARS coronavirus. BMC Syst Biol 10(1):93PubMed: 27663205 MGI: J:288523

Additional - Ppp1r14c^tm1Uhl related

Technical Support

CONTACT TECHNICAL SUPPORT

Genotyping Protocols
- Standard PCR:Ppp1r14c
- Genotyping resources and troubleshooting
Breeding Considerations

When maintaining a live colony, these mice can be bred as homozygotes. The Donating Investigator reports that the expected number of homozygotes are produced in heterozygous crosses.
- Additional Breeding and Husbandry Support
Citation
When using the B6;129S6-Ppp1r14c^tm1Uhl/J mouse strain in a publication, please cite the originating article(s) and include JAX stock #013041 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 wildtype for Ppp1r14c<tm1Uhl>

Related Products and Services

Frozen Mouse Embryo	B6;129S6-Ppp1r14c<tm1Uhl>/J	$2595.00
Frozen Mouse Embryo	B6;129S6-Ppp1r14c<tm1Uhl>/J	$2595.00
Frozen Mouse Embryo	B6;129S6-Ppp1r14c<tm1Uhl>/J	$3373.50
Frozen Mouse Embryo	B6;129S6-Ppp1r14c<tm1Uhl>/J	$3373.50

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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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Donating Investigator

Genetic overview

Research Applications

Base Price

Detailed Description

Development

Selected References

Ppp1r14ctm1Uhl

Allele Symbol: Ppp1r14ctm1Uhl

Disease Terms

Models with phenotypic similarity to human diseases where etiology is unknown or involving genes where ortholog is unknown.

Research Areas By Phenotype

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

Mammalian Phenotype Terms by Genotype

Genotype: Ppp1r14ctm1Uhl/Ppp1r14ctm1Uhlinvolves: 129S6/SvEvTac * C57BL/6J

behavior/neurological phenotype

integument phenotype

mammalian phenotype

mortality/aging

Genotype: Ppp1r14ctm1Uhl/Ppp1r14c+involves: 129S6/SvEvTac * C57BL/6J

behavior/neurological phenotype

Genotype: Ppp1r14ctm1Uhl/Ppp1r14ctm1UhlB6;129S6-Ppp1r14c/J

immune system phenotype

References

Additional References

Additional - Ppp1r14ctm1Uhl 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

Related Products and Services

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

Ppp1r14c^tm1Uhl

Allele Symbol: Ppp1r14c^tm1Uhl

Genotype: Ppp1r14c^tm1Uhl/Ppp1r14c^tm1Uhl
involves: 129S6/SvEvTac * C57BL/6J

Genotype: Ppp1r14c^tm1Uhl/Ppp1r14c⁺
involves: 129S6/SvEvTac * C57BL/6J

Genotype: Ppp1r14c^tm1Uhl/Ppp1r14c^tm1Uhl
B6;129S6-Ppp1r14c/J

Additional - Ppp1r14c^tm1Uhl related