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Strain Name:
C57BL/6-Prnpem1Aag Tg(PRNP)25109Evm/EvmMmjax
Stock Number:
075940-JAX
Citation ID:
RRID:MMRRC_075940-JAX
Other Names:
Tg25109

Strain Information

QUALITY CONTROL OF C57BL/6-Prnpem1Aag Tg(PRNP)25109Evm/EvmMmjax  |  The Jackson Laboratory
Last Updated:
Strain Data and Information Information by Submitter Assessed by MMRRC1,2
Published Provided
Allele-specific genotype3n.d.
Genetic backgroundn.d.
Viability of genotypes available for distributionn.d.
Specific Pathogen- Status n.d.
Recoverability of cryopreserved sperm/embryos4 n.d.
Gene or allele sequence3 n.d.
Gene or allele expression3n.d.
Gene or allele function3n.d.
Observable and/or measurable phenotypesn.d.
Fertility of genotypes available for distributionn.d.
Fecundity/breeding performance n.d.

1 When indicated as verified ("YES"), then please note that information presented is to the best of our knowledge correct and up-to-date at the time of verification at the MMRRC Distribution Center; however, this information is subject to change due to breeding, maintenance, and other actions on the mouse strain at the MMRRC Distribution Center; direct any questions on this table to the MMRRC Distribution Center for this mouse stain.

2 If verification has not been performed (as indicated by "NO"), investigators may request specific verification testing for a fee. Requests should be submitted directly to the MMRRC Distribution Center assigned to the management, archiving, and distribution of the strain. A full listing of available testing and analytical services is available at https://www.mmrrc.org/about/services.php.

3 This information may or may not apply to each individual engineered allele (e.g., Cre, FlpO) present in the strain.

4 Recovery refers to thawing, in vitro fertilization (IVF), and/or embryo culture leading to live offspring.

Prnpem1Aag
Name: prion protein; endonuclease-mediated mutation 1, Adriano Aguzzi
Type: Allele
Species: Mus musculus (mouse)
Chromosome: 2
Alteration at locus: TALEN
Prnp
Name: prion protein
Type: Gene
Species: Mesocricetus auratus (golden hamster)
Chromosome: unknown
PRNP
Name: prion protein (Kanno blood group)
Type: Gene
Species: Homo sapiens (human)
Chromosome: 20
Genetic Alterations
This PrnpZH3; Tg(PRNP)25109 double mutant mouse line harbors a mouse Prnp knock-out allele as well as full length human prion protein (PRNP) gene. These mice may be useful when studying neurodegenerative prion disease and validating PRNP protein targeting therapies.

Of note, the donating laboratory has also made a PrnpZH3; Tg(PRNP)26372 double mutant mouse line available as MMRRC:075939-JAX; where the transgene insertion site was determined to be on chromosome 18.
ES Cell Line
Not applicable
Phenotype

Prion diseases comprise a group of rare neurodegenerative disorders caused by accumulation of misfolded prion proteins. Prions are glycoproteins highly expressed in nervous tissues and play a role in cell signaling, copper metabolism, and neuroprotection. Mutations that lead to overexpression of the PRNP gene have been associated with spontaneous prion disease. The PrnpZH3; Tg(PRNP)25109 double mutant mouse line harbors a mouse prion protein (Prnp) knock-out allele as well as full length human prion protein (PRNP) transgene. Mice that are homozygous for the PrnpZH3 knock-out allele (MGI:5819099) do not express endogenous prion protein.

Mice that are homozygous for the PrnpZH3 knock-out allele and hemizygous for the Tg(PRNP)25109 transgene are viable and fertile with no overt phenotype. Mice that are homozygous for the Tg(PRNP)25109 transgene are generated at a lower than expected Mendelian ratio (~9%) from hemizygous x hemizygous matings. The donating laboratory confirmed the human PRNP transgene integrated ~3 tandem copies into chromosome 12, disrupting the endogenous FERM domain containing 6 (Frmd6) and thioredoxin-related transmembrane protein 1 (Tmx1) genes. The reduced viability of homozygous Tg(PRNP)25109 transgenic mice is thought to be caused by deletion of the Frmd6 gene. Surviving homozygous Tg(PRNP)25109 transgenic mice have ~2.0 fold increase in PRNP protein expression in the brain compared to wildtype. This PrnpZH3; Tg(PRNP)25109 mouse line may be used to test therapeutics targeting human PRNP. The donating laboratory typically utilizes mice that are homozygous for the PrnpZH3 knock-out allele and hemizygous for the Tg(PRNP)25109 transgene, which express PRNP protein at ~1.1 times the expression level in wildtype mice.

Of note, the donating laboratory has also made a PrnpZH3; Tg(PRNP)26372 double mutant mouse line available as MMRRC:075939-JAX; where the transgene insertion site was determined to be on chromosome 18 and demonstrates significantly higher PRNP expression in the brain compared to this PrnpZH3; Tg(PRNP)25109 mouse line.

Strain GQC Summary
Gene Specific Genotyping:

To request gene-specific and other genotyping services for a strain, please contact the distribution MMRRC Center for more information.

Background Genetic Quality:

The MMRRC has developed a Genetic Quality Control pipeline using the MiniMUGA array to provide additional information to identify and validate genetic backgrounds of MMRRC strains. For more information on whether genetic background data is available, please contact MMRRC_GeneticQC@med.unc.edu. Note: that MiniMUGA genetic background data is not available on all strains, but can be ordered if desired.

Suggested Control Mice
Littermates of all relevant genotypes.
  • Neurobiology
  • Research Tools
Submitter
Eric Minikel, Ph.D., Broad Institute.
Primary Reference

DOI: https://doi.org/10.1101/2024.12.05.627039

Strain Development
This PrnpZH3; Tg(PRNP)25109 double mutant mouse line harbors a mouse prion protein (Prnp) knock-out allele as well as full length human prion protein (PRNP) gene.

The human PRNP gene and flanking sequence were isolated from the RP11-715K24 bacterial artificial chromosome (BAC). The human sequence was cloned into the pStart-K plasmid by gap-repair cloning, with the p15A origin of replication and kanamycin resistance cassette located downstream of the gene, yielding a 48kb plasmid. The purified linearized DNA was microinjected into the pronuclei of fertilized C57BL/6 oocytes. Two founder lines were established and expanded, this line Tg(PRNP)25109 (MMRRC:075940-JAX) and Tg(PRNP)26372 available as MMRRC:075939-JAX. For founder line 25109, the donating laboratory confirmed the human PRNP transgene integrated ~3 tandem copies into chromosome 12, disrupting the endogenous FERM domain containing 6 (Frmd6) and thioredoxin-related transmembrane protein 1 (Tmx1) genes. While the exact breakpoint between the transgene and genome has not been identified, the integration was accompanied by two genomic deletions of 413kb and 62kb in which exons 1-8 of the Tmx1 gene and exons 2-14 of the Frmd6 gene are deleted.

Tg(PRNP)25109 transgenic mice were backcrossed to C57BL/6N mice for at least 5 generations and then crossed to PrnpZH3 knock-out mice (MGI:5819099), on a C57BL/6 background. The resulting PrnpZH3; Tg(PRNP)25109 double mutant mouse line was cryopreserved. To establish a live colony, an aliquot of frozen sperm was used to fertilize C57BL/6NJ oocytes.


Disclaimer: If MMRRC Strain Genetic Quality Control (GQC; based on MiniMUGA genotyping and analysis) has been completed for this strain, the information might differ from the genetic background information provided by the submitter. MiniMUGA genetic analysis is done on a strain’s tissue samples taken when archived by or ordered from the assigned MMRRC Center.

Colony and Husbandry Information

For more information about this colony's health status contact csmmrrc@jax.org
Coat Color
Black
Eye
Black
MMRRC Breeding System
Random intra-strain mating
Generation
N/A
Overall Breeding Performance
Good
Viability and Fertility: Female Male Comments
Homozygotes are viable: Reduced Reduced
Homozygotes are fertile: Reduced Reduced
Heterozygotes are fertile: Yes Yes
Age Reproductive Decline: 7 to 9 months 7 to 9 months
Average litter size
4 to 6
Recommended wean age
3 Weeks
Average Pups Weaned
4 to 6

Order Information

Limited quantities of breeder mice (up to 2 males and 2 females or 4 mice) per investigator per month are available from a live colony, usually available to ship in under 12 weeks. Larger quantities may be available, please contact the distributing center directly at csmmrrc@jax.org for more details.

Cryopreserved material may be available upon request, please inquire to csmmrrc@jax.org for more information.

Distribution of this strain requires submission of the MMRRC Conditions of Use (COU). A link to the COU web form will be provided via email after an order has been placed; the form should be completed then or the email forwarded to your institutional official for completion.

Additional charges may apply for any special requests. Shipping costs are in addition to the basic distribution/resuscitation fees. Information on shipping costs and any additional charges will be provided by the supplying MMRRC facility.

Click button to Request this one strain. (Use the MMRRC Catalog Search to request more than one strain.)
MMRRC Item # Description Distribution Fee / Unit (US $)
*Shipping & Handling not included*
Units Notes
075940-JAX-SPERM Cryo-preserved spermatozoa $473.00 / $473.00
Non-Profit / For-Profit
Aliquot Approximate quantity3
Cryopreserved material may be available upon request, please inquire to csmmrrc@jax.org for more information.

Some MMRRC strains were submitted by the submitter as cryopreserved germplasm, and because these strains were not cryopreserved by the MMRRC, we have not assessed the quality, nor genotype, of this material. Our expertise in reviving mice from various qualities of frozen sperm and embryos, using methods like IVF and ICSI, gives us confidence in successful recoveries in most cases. However, due to the uncertain quality of these samples, we'll limit revival attempts to two per order. Additional attempts are available for a fee, on top of standard charges, if requested. It's important to note that some strains may lack the expected mutation, so we can't assure successful order fulfillment until we attempt to revive the strain.

1 The distribution fee covers the expense of rederiving mice from a live mouse; you will receive the resulting litter. The litter will contain at minimum one mutant carrier; the actual number of animals and the gender and genotype ratios will vary. (Typically, multiple breeder pairs can be established from the recovered litter.) Prior to shipment, the MMRRC will provide information about the animals recovered. If you anticipate or find that you need to request specific genotypes, genders or quantities of mice in excess of what is likely from a resuscitated litter, you may discuss available options and pricing with the supplying MMRRC facility.

2 An aliquot contains a sufficient number of embryos (in one or more vials or straws and based on the transfer success rate of the MMRRC facility) to transfer into one to three recipients. The MMRRC makes no guarantee concerning embryo transfer success experienced in the recipient investigator's laboratory. Neither gender nor genotype ratios are guaranteed.

3 An aliquot is one straw or vial with sufficient sperm to recover at least one litter of mice, as per provided protocols, when performed at the MMRRC facility. The MMRRC makes no guarantee concerning the success of these procedures when performed outside the MMRRC facilities.

4 The distribution fee covers the expense of resuscitating mice from the cryo-archive; you will receive the resulting litter. The litter will contain at minimum one mutant carrier; the actual number of animals and the gender and genotype ratios will vary. (Typically, multiple breeder pairs can be established from the recovered litter.) Prior to shipment, the MMRRC will provide information about the animals recovered. If you anticipate or find that you need to request specific genotypes, genders or quantities of mice in excess of what is likely from a resuscitated litter, you may discuss available options and pricing with the supplying MMRRC facility.

To request material from the MMRRC: Please fill out our on-line request form (accessible from the catalog search results page, or click the Request this Strain button in the fees section). If you have questions or need assistance completing this form, you may call Customer Service at (800) 910-2291 (in USA or Canada) or (530) 757-5710 (international calls). Before you call, please have with you: the MMRRC item number, quantity needed, Bill-to and Ship-to contact information.