Overview

These prion protein-deficient mice are resistant to prion disease and serve as a PrP-deficient background for mouse models of spongiform encephalopathies and neurologic prion disorders.

Donating Investigator

Stanley Prusiner, University of California, San Francisco

Genetic overview

Genetic Background	Generation

Prnp^tm1Cwe

Allele Type	Gene Symbol	Gene Name
Targeted (Null/Knockout)	Prnp	prion protein

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Research Applications

Mouse/Human Gene Homologs
Cell Biology Research

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Base Price

Starting at:

$2,854.50 Domestic price Cryo Recovery

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Details

Detailed Description

A neo cassette replaces part of exon 3 of the prion protein (Prnp) gene in this strain, abolishing gene function. Prnp encodes the glycoprotein PrP^C which is attached to the external surface of central nervous system (CNS) neurons by a glycosylphosphatidyl inositol (GPI) anchor. Conformational changes in PrP^C to an infectious form, PrP^Sc, either by exogenous introduction or as a result of spontaneous mutation, have been linked to the development of spongiform encephalopathies such as scrapie in sheep and Creutzfeld-Jakob disease or GerstmannStraussler-Scheinker syndrome in man. These PrP^0/0 mice are viable and fertile. They exhibit decreased copper levels in the brain, impaired synaptic transmission, defective sleep-wake cycles, and altered circadian rhythms. When inoculated with PrP^Sc, PrP^0/0 mice are resistant to prion disease and do not replicate the infectious proteins. These mice serve as a PrP^C-deficient background for transgenic mice expressing GPI anchor defects (see (Stock No. 018124).

Development

A targeting vector was designed to replace part of exon 3 of the prion protein (Prnp) gene with a neomycin resistance (neo) cassette. The construct was electroporated into 129S7/SvEvBrd-Hprt⁺-derived AB1 embryonic stem (ES) cells. Correctly targeted ES cells were injected into C57BL/6J blastocysts and the resulting chimeric males were bred to C57BL/6J females. These Prnp^0/0 mice were backcrossed to C57BL/6J mice and subsequently to FVB/NCrl mice for 10 generations. Zygotes from these mice were microinjected with a transgene expressing PRNP lacking the GPI anchor signal (Tg(Prnp-tTA)F959Sbp). Upon arrival at The Jackson Laboratory, Tg959/Prnp^0/0 mice were bred to FVB/NJ (Stock No. 001800) for at least one generation. The Tg(Prnp-tTA)F959Sbp transgene was bred out and discarded. A colony of mice containing only the Prnp^0/0 allele was established.

Of note, another mouse line containing the Tg(Prnp-tTA)F959Sbp allele was imported and is maintained as Stock No. 018124.

Control Suggestions

Approximate Controls

001800 FVB/NJ

Additional Information

Considerations for Choosing Controls

Selected References

Bueler H; Fischer M; Lang Y; Bluethmann H; Lipp HP; DeArmond SJ; Prusiner SB; Aguet M; Weissmann C. 1992. Normal development and behaviour of mice lacking the neuronal cell-surface PrP protein [see comments] Nature 356(6370):577-82PubMed: 1373228 MGI: J:472

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Genetics

Prnp^tm1Cwe

Allele Symbol: Prnp^tm1Cwe

Allele Name	targeted mutation 1, Charles Weissmann
Allele Type	Targeted (Null/Knockout)
Allele Synonym(s)	Prnp^tm1Cwe; targeted mutation 1, Charles Weissmann
Gene Symbol and Name	Prnp, prion protein
Gene Synonym(s)	PrPSc; AI325101; AltPrP; prion protein, structural locus; Sinc; CD230; GSS; AA960666; Sinc; Prn-i; Prn-p; PrP27-30; PrP33-35C; PrPC; PRIP; Prn-i; Prn-p; PrP; ASCR; expressed sequence AA960666; p27-30; expressed sequence AI325101; CJD; KURU; prion protein, scrapie incubation time regulation; scrapie incubation period; Prn; PrPc
Strain of Origin	129S7/SvEvBrd-Hprt⁺
Chromosome	2
Molecular Note	A 552 bp fragment of the coding region contained within exon 3 was replaced with a 1.1 kb cassette containing the TK promoter followed by the neomycin gene.
Mutations Made By	Stanley Prusiner, University of California, San Francisco

Disease/Phenotype

Disease Terms

No similarity to the expected human disease phenotype was found. One or more human genes are associated with this human disease. The mouse genotype may involve mutations to orthologs of one or more of these genes, but the phenotype did not resemble the disease.

Research Areas By Genotype

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

Mouse/Human Gene Homologs
Cell Biology Research
- Protein Processing

Mammalian Phenotype Terms by Genotype

The following phenotype information is associated with a similar, but not exact match to this JAX^® Mice strain

Genotype: Prnp^tm1Cwe/Prnp^tm1Cwe
involves: 129S7/SvEvBrd * C57BL/6

homeostasis/metabolism phenotype

decreased brain copper level
- after 12 months, copper levels in the brain fail to increase with age unlike in wild-type mice
- copper levels in the synaptosomes are decreased compared to in wild-type mice

mammalian phenotype

behavior/neurological phenotype
- Normal - no ataxia or Purkinje cell loss observed
- Normal - normal behavior

nervous system phenotype

abnormal CNS synaptic transmission
- GABA(A) receptor-mediated fast inhibition is weaker in hippocampal slices of mutants than in wild-type mice, indicating impaired synaptic inhibition

abnormal inhibitory postsynaptic currents
- inhibitory postsynaptic currents (ipscs) have significantly slower rising phases and are slower

abnormal inhibitory postsynaptic potential
- fast inhibitory postsynaptic potentials (ipsps) appear weaker in hippocampal slices than in wild-type, however excitatory postsynaptic potentials are normal

decreased brain copper level
- after 12 months, copper levels in the brain fail to increase with age unlike in wild-type mice
- copper levels in the synaptosomes are decreased compared to in wild-type mice

reduced long term potentiation
- long term potentiation in CA1 of hippocampal slices is weaker in both the absence and presence of bicuculline

References

Bueler H; Fischer M; Lang Y; Bluethmann H; Lipp HP; DeArmond SJ; Prusiner SB; Aguet M; Weissmann C. 1992. Normal development and behaviour of mice lacking the neuronal cell-surface PrP protein [see comments] Nature 356(6370):577-82PubMed: 1373228 MGI: J:472

Additional - Prnp^tm1Cwe related

Technical Support

Contact Technical Support

Genotyping Protocols
- Separated PCR: Prnp^tm1Cwe
- Separated MCA: Prnp^tm1Cwe
- Genotyping resources and troubleshooting
Breeding Considerations

When maintaining a live colony, homozygous mice may be bred together.
- Additional Breeding and Husbandry Support
Citation
When using the FVB.129S7(B6)-Prnp^tm1Cwe/J mouse strain in a publication, please cite the originating article(s) and include JAX stock #018122 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	Genotype	Price
	Heterozygous for Prnp<tm1Cwe>

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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Frozen Mouse Embryo

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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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General Terms and Conditions

Questions about Terms of Use

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Licensing Information

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Donating Investigator

Genetic overview

Research Applications

Base Price

Detailed Description

Development

Control Suggestions

Approximate Controls

Additional Information

Selected References

Prnptm1Cwe

Allele Symbol: Prnptm1Cwe

Disease Terms

No similarity to the expected human disease phenotype was found. One or more human genes are associated with this human disease. The mouse genotype may involve mutations to orthologs of one or more of these genes, but the phenotype did not resemble the disease.

Research Areas By Genotype

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

Mammalian Phenotype Terms by Genotype

Genotype: Prnptm1Cwe/Prnptm1Cweinvolves: 129S7/SvEvBrd * C57BL/6

homeostasis/metabolism phenotype

mammalian phenotype

nervous system phenotype

References

Additional - Prnptm1Cwe 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

Additional Use Restrictions Apply

Licensing Information

JAX® Mice, Products & Services Conditions of Use

No Warranty

Credit for PRODUCTS or SERVICES

Animal Care and Use for SERVICES

No Liability

Prnp^tm1Cwe

Allele Symbol: Prnp^tm1Cwe

Genotype: Prnp^tm1Cwe/Prnp^tm1Cwe
involves: 129S7/SvEvBrd * C57BL/6

Additional - Prnp^tm1Cwe related