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.

The hAbeta-loxP-KI allele is available on a C57BL/6J congenic background (Stock No. 031051), on a C57BL/6NJ congenic background (Stock No. 032013) and on a mixed C57BL/6J and C57BL/6NJ background (Stock No. 030898).

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 4-week

510.00 Domestic price for breeder pair

View Price List

Details

Detailed Description

hAbeta-loxP-KI knock-in is a mutant "humanized" App allele in which three mutations were introduced into the mouse App exon that encodes the Aβ fragment (see below), such that the sequence now encodes the same amino acids as human. This exon is also flanked by loxP sites. These hAbeta-loxP-KI 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.

The hAbeta-loxP-KI allele is available on a C57BL/6J congenic background (Stock No. 031051), on a C57BL/6NJ congenic background (Stock No. 032013) and on a mixed C57BL/6J and C57BL/6NJ background (Stock No. 030898).

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 (Aβ-encoding amino acids 5 (G->R), 10 (F->Y) and 13 (R->H)). 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 Phenotype

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
- 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/Product	Description	Price
	Heterozygous for App<tm1.1Lfa>

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

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

"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"). "PRODUCT(S)" means biological materials supplied by JACKSON, and their derivatives. "SERVICES" means projects conducted by JACKSON for other parties that may include but are not limited to the use of MICE or PRODUCTS. "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 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, PRODUCTS or SERVICES from JACKSON shall be deemed as agreement by RECIPIENT to these conditions, and departure from these conditions requires JACKSON’s prior written authorization.

No Warranty

MICE, PRODUCTS AND SERVICES ARE PROVIDED "AS IS". JACKSON EXTENDS NO WARRANTIES OF ANY KIND, EITHER EXPRESS, IMPLIED, OR STATUTORY, WITH RESPECT TO MICE, PRODUCTS OR SERVICES, INCLUDING ANY IMPLIED WARRANTY OF MERCHANTABILITY OR FITNESS FOR A PARTICULAR PURPOSE, OR ANY WARRANTY OF NON-INFRINGEMENT OF ANY PATENT, TRADEMARK, OR OTHER INTELLECTUAL PROPERTY RIGHTS.

Credit for PRODUCTS or SERVICES

In case of dissatisfaction for a valid reason and claimed in writing by a purchaser within ninety (90) days of receipt of, PRODUCTS or SERVICES, JACKSON will, at its option, provide credit or replacement for the PRODUCT received or the SERVICES provided; JACKSON makes no other representations and this shall be the exclusive remedy of the purchaser. Please note specific policy for live mice.

Animal Care and Use for SERVICES

Consistent with the requirement for a written understanding regarding animal care and use, the JACKSON Animal Care and Use Committee will review the animal care and use protocol(s) associated with any SERVICES to be performed at JACKSON, and JACKSON shall have ultimate responsibility and authority for the care of animals while on site or in JACKSON custody.

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. Unless prohibited by law, 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, PRODUCTS or SERVICES 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.

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 Phenotype

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