Overview

Homozygous App mice weigh 15%-20% less than age-matched wild-type controls, and exhibit decreased locomotor activity and forelimb grip strength. Reactive gliosis is seen in some homozygous mice at 14 weeks of age. This beta-amyloid precursor protein (APP) knock-out strain offers a model useful in studies related to Alzheimer's disease.

Donating Investigator

Dr. David R Borchelt, University of Florida

Genetic overview

Genetic Background	Generation
	N10+N9F9 (2018-12-12 00:00:00)

App^tm1Dbo

Allele Type	Gene Symbol	Gene Name
Targeted (Null/Knockout)	App	amyloid beta (A4) precursor protein

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Research Applications

Neurobiology Research
Mouse/Human Gene Homologs

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Base Price

Starting at:

$236.78 Domestic price for female

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Details

Detailed Description

At birth, mice homozygous for the targeted allele are viable, and do not display any gross physical or behavioral abnormalities. No App gene product (mRNA or protein) is detected. Body weight is 15-20% less than that observed in wildtype age-matched control mice. By 14 weeks of age the mice exhibit evidence of reactive gliosis. Neurological evaluation reveals significantly reduced forelimb grip strength and decreased locomotor activity. This mutant strain offers a model useful in studies related to Alzheimer's disease.

Development

A targeting vector containing neomycin resistance and herpes simplex virus thymidine kinase genes was used to disrupt a region of the App gene encoding the promoter and exon 1. The construct was electroporated into 129S7/SvEvBrd-derived AB2.1 embryonic stem (ES) cells. Correctly targeted ES cells were injected into C57BL/6J blastocysts. The resulting chimeric animals were backcrossed to C57BL/6J mice.

Control Suggestions

000664 C57BL/6J

Additional Information

Considerations for Choosing Controls

Selected References

Zheng H; Jiang M; Trumbauer ME; Sirinathsinghji DJ; Hopkins R; Smith DW; Heavens RP; Dawson GR; Boyce S; Conner MW; Stevens KA; Slunt HH; Sisodia SS; Chen HY; Van der Ploeg LHT. 1995. beta-Amyloid precursor protein-deficient mice show reactive gliosis and decreased locomotor activity. Cell 81(4):525-31PubMed: 7758106 MGI: J:25512

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Genetics

App^tm1Dbo

Allele Symbol: App^tm1Dbo

Allele Name	targeted mutation 1, David R Borchelt
Allele Type	Targeted (Null/Knockout)
Allele Synonym(s)	targeted mutation 1, David R Borchelt; App^tm1Dbo
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	129S7/SvEvBrd-Hprt^b-m2
Chromosome	16
Molecular Note	A neomycin resistance cassette replaced a 3.8 kb sequence including the promoter region and first exon. Northern blot analysis did not detect mRNA in brain or kidney of homozygous mutant mice.
Mutations Made By	Dr. David Borchelt, University of Florida

Disease/Phenotype

Disease Terms

Model with phenotypic similarity to human disease where etiologies involve orthologs. Human genes are associated with this disease. Orthologs of those genes appear in the mouse genotype(s).

Alzheimer's disease

Research Areas By Genotype

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

Genotype: App^tm1Dbo related

Neurobiology Research
- Neurodegeneration
- Alzheimer's Disease
Mouse/Human Gene Homologs
- Alzheimer's

Mammalian Phenotype Terms by Genotype

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

Genotype: App^tm1Dbo/App^tm1Dbo
involves: 129S7/SvEvBrd * C57BL/6J

behavior/neurological phenotype

abnormal active avoidance behavior
- age-related impairment in conditioned avoidance tests, seen at 10 months of age, but not at 4 months of age

abnormal locomotor activation
- decreased locomotor activity

abnormal spatial learning
- impairment in watermaze test of spatial learning, both at 4 and 10 months of age

decreased grip strength
- significantly reduced grip strength

hypoactivity

nervous system phenotype

abnormal long term potentiation
- impairment of ability of high frequency stimuli to induce LTP which correlated with extent of gliosis in stratum radiatum

abnormal neuron morphology
- the branching of dendrites of both cortical and hippocampal neurons was much less extensive, however did not show any loss of cells in the cortex or the hippocampus

astrocytosis
- reactive astrocytosis in many brain areas, but predominantly in the cortex and hippocampus at 14 weeks of age

gliosis
- reactive gliosis was observed throughout the cortical layers of the neocortex and extensive astrogliosis was seen in the CA1 region of the hippocampus, however did not observe neuronal cell damage

intracerebral hemorrhage
- hematomas are smaller following experimentally induced intracerebral hemorrhage as compared to wild-type, but are larger than homozygous App^tm1.1Wevn mice

cardiovascular system phenotype

hematoma
- hematomas are smaller following experimentally induced intracerebral hemorrhage as compared to wild-type, but are larger than homozygous App^tm1.1Wevn mice

intracerebral hemorrhage
- hematomas are smaller following experimentally induced intracerebral hemorrhage as compared to wild-type, but are larger than homozygous App^tm1.1Wevn mice

growth/size/body region phenotype

decreased body weight
- body weight was 15-20% less at all ages compared with that of controls

homeostasis/metabolism phenotype

altered susceptibility to induced thrombosis
- time to cessation of blood flow following induced carotid artery thrombosis is decreased as compared to wild-type and homozygous App^tm1.1Wevn mice

References

Zheng H; Jiang M; Trumbauer ME; Sirinathsinghji DJ; Hopkins R; Smith DW; Heavens RP; Dawson GR; Boyce S; Conner MW; Stevens KA; Slunt HH; Sisodia SS; Chen HY; Van der Ploeg LHT. 1995. beta-Amyloid precursor protein-deficient mice show reactive gliosis and decreased locomotor activity. Cell 81(4):525-31PubMed: 7758106 MGI: J:25512

Additional References

von Koch CS; Zheng H; Chen H; Trumbauer M; Thinakaran G; van der Ploeg LH; Price DL; Sisodia SS. 1997. Generation of APLP2 KO mice and early postnatal lethality in APLP2/APP double KO mice. Neurobiol Aging 18(6):661-9PubMed: 9461064 MGI: J:45851

Additional - App^tm1Dbo related

Technical Support

Contact Technical Support

Genotyping Protocols
- MELT: App^{tm1 Dbo} MCA SEP
- Genotyping resources and troubleshooting
Dietary Information
- LabDiet® 5K52 formulation (6% fat)
Breeding Considerations

This strain originated on a B6;129S7 background and has been backcrossed to C57BL/6J for at least ten generations (7/01). Coat color expected from breeding:Black
- Additional Breeding and Husbandry Support
Mating System
- Homozygote x Homozygote
Citation
When using the B6.129S7-App^tm1Dbo/J mouse strain in a publication, please cite the originating article(s) and include JAX stock #004133 in your Materials and Methods section.

Animal Health Reports

Facility Barrier Level Descriptions

FGB29 (Standard)

Pricing & Availability

Available

Domestic
International

Live Mouse

Age

Genotype

Price

weeks

Cryorecovery - Not-For-Profit & Academic Pricing

Service	Genotype	Price
	Heterozygous or Wild-type for App<tm1Dbo>

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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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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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

Additional Information

Selected References

Apptm1Dbo

Allele Symbol: Apptm1Dbo

Disease Terms

Model with phenotypic similarity to human disease where etiologies involve orthologs. Human genes are associated with this disease. Orthologs of those genes appear in the mouse genotype(s).

Research Areas By Genotype

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

Genotype: Apptm1Dbo related

Mammalian Phenotype Terms by Genotype

Genotype: Apptm1Dbo/Apptm1Dboinvolves: 129S7/SvEvBrd * C57BL/6J

behavior/neurological phenotype

nervous system phenotype

cardiovascular system phenotype

growth/size/body region phenotype

homeostasis/metabolism phenotype

References

Additional References

Additional - Apptm1Dbo related

Genotyping Protocols

Dietary Information

Breeding Considerations

Mating System

Citation

Animal Health Reports

Live Mouse

Cryorecovery - Not-For-Profit & Academic Pricing

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^tm1Dbo

Allele Symbol: App^tm1Dbo

Genotype: App^tm1Dbo related

Genotype: App^tm1Dbo/App^tm1Dbo
involves: 129S7/SvEvBrd * C57BL/6J

Additional - App^tm1Dbo related