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 Heterozygote x Heterozygote         (Female x Male)   11-JUL-09 Species laboratory mouse Generation N7 (22-OCT-09)   Donating Investigator IMR Colony,   The Jackson Laboratory

Description
These mice possess loxP sites on either side of exon 7 of the targeted gene. Mice that are homozygous for this allele are viable, fertile, normal in size and do not display any gross physical or behavioral abnormalities. When these "floxed" mice are bred to mice that express Cre recombinase, resulting offspring can have one of three resulting genotypes (only exon 7 deleted, only the neo selection cassette deleted, or both exon 7 and the neo selection cassette deleted) in the cre-expressing tissue(s). These PS1-floxed mice may be useful in generating conditional knockouts of Presenilin 1 for studying Alzheimer's Disease.

For example, when crossed to a strain expressing Cre recombinase in postnatal neurons (see Stock No. 006143), this mutant mouse strain may be useful in studies of amyloid plaque formation.

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. It should be noted that the phenotype could vary from that originally described. We will modify the strain description if necessary as published results become available.

Development
A loxP site flanked targeting vector containing a neomycin resistance gene was utilized in the construction of this mutant. This selection cassette was inserted downstream of exon 7 of the targeted gene, and another loxP site was inserted upstream of exon 7. This construct was electroporated into 129P2/OlaHsd derived E14 embryonic stem (ES). Homozygotes on a mixed B6;129P2 genetic background were sent to The Jackson Laboratory (as Stock No. 007605). Upon arrival, some mice were backcrossed to C57BL/6J inbred mice (Stock No. 000664) for at least 5 generations to generate this congenic strain (Stock No. 007685)(see note below).

NOTE: For the parental strain (Stock No. 007605), a 27 SNP (single nucleotide polymorphism) panel analysis performed by The Jackson Laboratory revealed a single loci that typed as homozygous for 129/P strain type (Chromosome 12 approximately 9.8 cM) and three additional loci that were segregating for either C57BL/6J or 129/P strain type (Chromosome 1 approximately 52.0 cM, Chromosome 4 approximately 10.9 cM, and Chromosome 8 approximately 4.4 cM). These loci are to be monitored and attempted to be changed to C57BL/6J-like during the backcrossing protocol to generate the congenic strain (Stock No. 007685). Because the targeted mutation also resides on chromosome 12, that loci may remain as 129/P strain type even after backcrossing (August 2008).

Control Information

	Control
	Wild-type from the colony
	000664 C57BL/6J
Considerations for Choosing Controls

Related Strains

Strains carrying   Psen1^tm1Vln allele

007605

B6;129P-Psen1tm1Vln/J

View Strains carrying   Psen1^tm1Vln     (1 strain)

Strains carrying other alleles of Psen1

004193	B6.129-Psen1tm1Mpm/J
003615	B6.129-Psen1tm1Shn/J
004807	B6;129-Psen1tm1Mpm Tg(APPSwe,tauP301L)1Lfa/J
003822	B6;129S-Psen1tm1Shn/J

View Strains carrying other alleles of Psen1     (4 strains)

Additional Web Information

Introduction to Cre-lox technology
Visit the Alzheimer's Disease Mouse Model Resource site for helpful information on Alzheimer's Disease and research resources.

Phenotype

Phenotype Information

View Related Disease (OMIM) Terms

Related Disease (OMIM) Terms

	Alzheimer Disease 3 - Models with phenotypic similarity to human disease where etiologies involve orthologs.1
	Alzheimer Disease; AD - 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.

Psen1^tm1Vln/Psen1^tm1Vln

        Background Not Specified

• normal phenotype
• no abnormal phenotype detected (MGI Ref ID J:87229)

The following phenotype relates to a compound genotype created using this strain.
Contact JAX^® Services jaxservices@jax.org for customized breeding options.

Psen1^tm1Vln/Psen1^tm1Vln Tg(Thy1-cre)1Vln/0

        involves: FVB/N   (conditional)

• behavior/neurological phenotype
• *normal* behavior/neurological phenotype (MGI Ref ID J:87229)
  • mice do not display any behavioral or cognitive deficits
• nervous system phenotype
• *normal* nervous system phenotype (MGI Ref ID J:87229)
  • brains of 6 month-old mice do not show any morphological abnormalities like cerebral hemorrhages, cavities or tumors; no defects are observed up to 2 years of age
• abnormal long term potentiation (MGI Ref ID J:87229)
  • initial phase of the slope of fEPSP is lower (168% vs 221% in controls) 15 minutes after tetanic stimulation; slope of fEPSP progressively increases to approach control levels 2 hours following stimulation
• amyloid beta deposits (MGI Ref ID J:87229)
  • levels of amyloid beta-40 and -42 (Abeta40, Abeta42) are reduced relative to controls; C-terminal fragments of APP accumulate in brains
• other phenotype
• amyloid beta deposits (MGI Ref ID J:87229)
  • levels of amyloid beta-40 and -42 (Abeta40, Abeta42) are reduced relative to controls; C-terminal fragments of APP accumulate in brains

View Research Applications

Research Applications

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

Mouse/Human Gene Homologs
Alzheimer's

Neurobiology Research
Alzheimer's Disease
Behavioral and Learning Defects

Research Tools
Cre-lox System
      loxP-flanked Sequences

Genes & Alleles

Gene & Allele Information

Allele Symbol		Psen1tm1Vln
Allele Name		targeted mutation 1, Fred Van Leuven
Allele Type		Targeted (Floxed/Frt)
Common Name(s)		PS1-flox;
Mutation Made By		Fred Van Leuven,   Katholieke Universiteit Leuven
Strain of Origin		129P2/OlaHsd
ES Cell Line Name		E14
ES Cell Line Strain		129P2/OlaHsd
Gene Symbol and Name		Psen1, presenilin 1
Chromosome		12
Gene Common Name(s)		AD3; Ad3h; FAD; PS-1; PS1; S182; alzheimer disease 3 homolog; presenilin-1;
Molecular Note		Exon 7 was flanked by a single loxP site in intron 6 and floxed neo cassette in intron 7. [MGI Ref ID J:87229]

Genotyping

Genotyping Information

This strain will not have a genotyping protocol or one is not currently available.

Helpful Links

Genotyping resources and troubleshooting

References

References

Selected Reference(s)

Dewachter I; Reverse D; Caluwaerts N; Ris L; Kuiperi C; Van den Haute C; Spittaels K; Umans L; Serneels L; Thiry E; Moechars D; Mercken M; Godaux E; Van Leuven F. 2002. Neuronal deficiency of presenilin 1 inhibits amyloid plaque formation and corrects hippocampal long-term potentiation but not a cognitive defect of amyloid precursor protein [V717I] transgenic mice. J Neurosci 22(9):3445-53. [PubMed: 11978821]  [MGI Ref ID J:87229]

Additional References

Psen1^tm1Vln related

Dewachter I; Ris L; Croes S; Borghgraef P; Devijver H; Voets T; Nilius B; Godaux E; Van Leuven F. 2008. Modulation of synaptic plasticity and Tau phosphorylation by wild-type and mutant presenilin1. Neurobiol Aging 29(5):639-52. [PubMed: 17222948]  [MGI Ref ID J:137684]

Herms J; Schneider I; Dewachter I; Caluwaerts N; Kretzschmar H; Van Leuven F. 2003. Capacitive calcium entry is directly attenuated by mutant presenilin-1, independent of the expression of the amyloid precursor protein. J Biol Chem 278(4):2484-9. [PubMed: 12431992]  [MGI Ref ID J:81726]

Ris L; Dewachter I; Reverse D; Godaux E; Van Leuven F. 2003. Capacitative calcium entry induces hippocampal long term potentiation in the absence of presenilin-1. J Biol Chem 278(45):44393-9. [PubMed: 12902342]  [MGI Ref ID J:86553]

Tamboli IY; Prager K; Thal DR; Thelen KM; Dewachter I; Pietrzik CU; St George-Hyslop P; Sisodia SS; De Strooper B; Heneka MT; Filippov MA; Muller U; van Leuven F; Lutjohann D; Walter J. 2008. Loss of gamma-secretase function impairs endocytosis of lipoprotein particles and membrane cholesterol homeostasis. J Neurosci 28(46):12097-106. [PubMed: 19005074]  [MGI Ref ID J:142399]

Health & husbandry

Health & Colony Maintenance Information

Animal Health Reports

Room Number           AX11

Colony Maintenance

Breeding & Husbandry	Mutant mice were bred to C57BL/6J inbred mice (Stock No. 000664) for many generations to establish this congenic strain. When maintaining the live congenic colony, heterozygous or homozygous mice may be bred together.
Mating System	Heterozygote x Heterozygote         (Female x Male)   11-JUL-09
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
	Wild-type from the colony
	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.

Payment Terms and Conditions

Terms are granted by individual review and stated on the customer invoice(s) and account statement. These transactions are payable in U.S. currency within the granted terms. Payment for services, products, shipping containers, and shipping costs that are rendered are expected within the payment terms indicated on the invoice or stated by contract. Invoices and account balances in arrears of stated terms may result in The Jackson Laboratory pursuing collection activities including but not limited to outside agencies and court filings.

See Terms of Use tab for General Terms and Conditions

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.

---

Ordering and Purchasing Information

      Purchasing Information
      JAX^® Mice Orders
      Surgical Services

Contact Information
Orders & Technical Support
Tel: 1-800-422-6423 or 1-207-288-5845
Fax: 1-207-288-6150
Technical Support Email Form

Terms of Use

Terms of Use

General Terms and Conditions

For Licensing and Use Restrictions view the link(s) below:
- Use of MICE by companies or for-profit entities requires a license prior to shipping.

Contact information

General inquiries

Contracts Administration

phone:	207-288-6470
fax:	207-288-6655

JAX^® Mice, Products & Services Conditions of Use

"MICE" means mouse strains, their progeny derived by inbreeding or crossbreeding, unmodified derivatives from mouse strains or their progeny supplied by The Jackson Laboratory ("JACKSON"). "PRODUCTS" means biological materials supplied by JACKSON, and their derivatives. "RECIPIENT" means each recipient of MICE, PRODUCTS, or services provided by JACKSON including each institution, its employees and other researchers under its control. MICE or PRODUCTS shall not be: (i) used for any purpose other than the internal research, (ii) sold or otherwise provided to any third party for any use, or (iii) provided to any agent or other third party to provide breeding or other services. Acceptance of MICE or PRODUCTS from JACKSON shall be deemed as agreement by RECIPIENT to these conditions, and departure from these conditions requires JACKSON's prior written authorization.

In case of dissatisfaction for a valid reason and claimed in writing by a purchaser within ninety (90) days of receipt of mice, products or services, JACKSON will, at its option, provide credit or replacement for the mice or product received or the services provided.

No Liability

In no event shall JACKSON, its trustees, directors, officers, employees, and affiliates be liable for any causes of action or damages, including any direct, indirect, special, or consequential damages, arising out of the provision of MICE, PRODUCTS or services, including economic damage or injury to property and lost profits, and including any damage arising from acts or negligence on the part of JACKSON, its agents or employees. In purchasing or receiving MICE, PRODUCTS or services from JACKSON, purchaser or recipient, or any party claiming by or through them, expressly releases and discharges JACKSON from all such causes of action or damages, and further agrees to defend and indemnify JACKSON from any costs or damages arising out of any third party claims.

MICE and PRODUCTS are to be used in a safe manner and in accordance with all applicable governmental rules and regulations.

The foregoing represents the General Terms and Conditions applicable to JACKSON’s MICE, PRODUCTS or services. In addition, special terms and conditions of sale of certain MICE, PRODUCTS or services may be set forth separately in JACKSON web pages, catalogs, price lists, contracts, and/or other documents, and these special terms and conditions shall also govern the sale of these MICE, PRODUCTS and services by JACKSON, and by its licensees and distributors.

Acceptance of delivery of MICE, PRODUCTS or services shall be deemed agreement to these terms and conditions. No purchase order or other document transmitted by purchaser or recipient that may modify the terms and conditions hereof, shall be in any way binding on JACKSON, and instead the terms and conditions set forth herein, including any special terms and conditions set forth separately, shall govern the sale of MICE, PRODUCTS or services by JACKSON.