Overview

Also Known As: hAbeta-loxP-KI on mixed B6J and B6NJ

This "humanized" App knock-in strain in which 3 point mutations were introduced into exon 14 of the mouse App gene produces a mutant protein that is expected to more readily aggregate. Exon 14 is also flanked by loxP sites. This strain may be useful for studying late-onset sporadic Alzheimer’s disease.

hAbeta-loxP-KI mice are also available on a C57BL/6NJ congenic background (Stock No. 032013).

Donating Investigator

Frank LaFerla, University of California, Irvine

Genetic overview

Genetic Background	Generation
	?+pN1 (2018-09-17 00:00:00)

App^tm1.1Aduci

Allele Type	Gene Symbol	Gene Name
Targeted (Conditional ready (e.g. floxed), Humanized sequence)	App	amyloid beta (A4) precursor protein

View Genetics

Research Applications

Neurobiology Research

View All Research Applications

Base Price

Starting at:

$255.00 Domestic price for female

510.00 Domestic price for breeder pair

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Details

Detailed Description

These hAbeta-loxP-KI knock-in mice, express a mutant "humanized" App allele in which mutations were introduced into exon 14. Exon 14 is flanked by loxP sites. These mice express mouse APP protein with a “humanized” amyloid beta peptide sequence. Homozygotes are viable and fertile. As the mice are characterized, we will modify the strain description and add phenotype data.

Important note about App isoforms and exon numbering: The App-201 isoform (695 aa protein) is encoded by 16 exons, of which the Abeta sequence is encoded by exon 14. The App-206 isoform (770 aa protein) is encoded by 18 exons, of which the Abeta sequence is encoded by exon 16.

Development

The mouse BAC RP23-424A20, containing the entire App gene, was used to amplify and subclone a 3.6kb KpnI – PacI region containing App exon 14 (ENSMUSE00000131684). The Abeta coding sequence within exon 14 was modified by changing three bases to produce three amino acid substitutions (amino acids 5 (G->R), 10 (F->Y) and 13 (R->H)) in exon 14, and loxP sites were added to flank exon 14 and a FRT site flanked neo selection cassette (pM-30) was used to enable G418-selection in mouse ES cells. The targeting vector was electroporated into C57BL/6N derived JM8.N4 ES cells. Correctly targeted ES cells were injected into blastocysts. The resulting chimeric male animals were bred to Actin-FLPe transgenic female mice, N5 on C57BL/6NTac, (see for example, Stock No. 005703), to remove the neo selection cassette. Male offspring mice that no longer carried the selection cassette were then bred to C57BL/6J females to remove the Tg(ACTFLPe)9205Dym transgene. The mice were then intercrossed to produce homozygotes that were subsequently intercrossed for 7 to 8 generations to generate homozygotes. The mice were then bred to C57BL/6NTac wild-type mice once. Heterozygotes were intercrossed to generate homozygotes for the hAbeta-loxP-KI (APPKI-hAbwt) allele that are also homozygous for wild-type Nnt.
Upon arrival, sperm was cryopreserved. To establish our live colony, an aliquot of frozen sperm was used to fertilize C57BL/6NJ oocytes (Stock No. 005304). This strain is on a mixed B6J and B6N genetic background.

Control Suggestions

Approximate Controls

005304 C57BL/6NJ

Additional Information

Considerations for Choosing Controls

Genetics

App^tm1.1Aduci

Allele Symbol: App^tm1.1Aduci

Allele Name	targeted mutation 1.1, Frank LaFerla
Allele Type	Targeted (Conditional ready (e.g. floxed), Humanized sequence)
Allele Synonym(s)	App^tm1.1Aduci; targeted mutation 1.1, Frank LaFerla
Gene Symbol and Name	App, amyloid beta (A4) precursor protein
Gene Synonym(s)	Cvap; E030013M08Rik; betaAPP; Alzheimer disease amyloid beta protein; E030013M08Rik; Adap; ABETA; APPI; ABPP; AD1; AL024401; CTFgamma; PN-II; PN2; cerebrovascular amyloid peptide; CVAP; appican; Adap; protease nexin II; AAA; expressed sequence AL024401; RIKEN cDNA E030013M08 gene; Abeta; Cvap; preA4
Strain of Origin	C57BL/6N
Chromosome	16
Molecular Note	The targeting construct includes a loxP site upstream of exon 14, 3 point mutations inserted into exon 14 to create amino acid substitutions (amino acids 5 (G->R), 10 (F->Y) and 13 (R->H)) (ENSMUSE00000131684), a loxP site downstream of exon 14 and a FRT-flanked neo selection cassette, which is removed by FLP-mediated recombination.

Disease/Phenotype

Disease Terms

Research Areas By Genotype

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

Neurobiology Research
- Alzheimer's Disease
  - APP and PSEN1 mutants

Mammalian Phenotype Terms by Genotype

References

Additional - App^tm1.1Aduci related

Technical Support

Contact Technical Support

Genotyping Protocols
- Standard PCR:App^tm1.1Aduci
- Genotyping resources and troubleshooting
Breeding Considerations

When maintaining a live colony, these mice can be bred as homozygotes.
- Additional Breeding and Husbandry Support
Mating System
- Homozygote x Homozygote
Citation
When using the hAbeta-loxP-KI on mixed B6J and B6NJ mouse strain in a publication, please cite the originating article(s) and include JAX stock #030898 in your Materials and Methods section.

Animal Health Reports

Facility Barrier Level Descriptions

AX11 (Maximum)

Pricing & Availability

Available

Domestic
International

Live Mouse

Age

Genotype

Price

weeks

Breeder Pair

Sex

Genotype

Price

Female
Male

Cryorecovery - Pricing

Service	Genotype	Price
	Heterozygous for App<tm1.1Lfa>

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.

Related Products and Services

Frozen Mouse Embryo	B6(SJL)-App<tm1.1Aduci>/J	$2595.00
Frozen Mouse Embryo	B6(SJL)-App<tm1.1Aduci>/J	$2595.00
Frozen Mouse Embryo	B6(SJL)-App<tm1.1Aduci>/J	$3373.50
Frozen Mouse Embryo	B6(SJL)-App<tm1.1Aduci>/J	$3373.50

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.

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.

Terms Of Use

Terms of Use

General Terms and Conditions

Questions about Terms of Use

Additional Use Restrictions Apply

Notice regarding distribution of this strain.

Licensing Information

Phone: 207-288-6470

Email: TechTran@jax.org

JAX® Mice, Products & Services Conditions of Use

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Animal Care and Use for SERVICES

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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.

Also Known As: hAbeta-loxP-KI on mixed B6J and B6NJ

Donating Investigator

Genetic overview

Research Applications

Base Price

Detailed Description

Development

Control Suggestions

Approximate Controls

Additional Information

Apptm1.1Aduci

Allele Symbol: Apptm1.1Aduci

Disease Terms

Research Areas By Genotype

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

Mammalian Phenotype Terms by Genotype

References

Additional - Apptm1.1Aduci related

Genotyping Protocols

Breeding Considerations

Mating System

Citation

Animal Health Reports

Live Mouse

Breeder Pair

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

App^tm1.1Aduci

Allele Symbol: App^tm1.1Aduci

Additional - App^tm1.1Aduci related