Overview

Also Known As:p97FE65 KO

These Apbb1 knock-out mice exhibit slower learning rates on memory tasks and severe impairments in spatial memory extinction. They are suitable for use in applications related to the study of Alzheimer's disease and other learning/memory applications.

Donating Investigator

Qubai Hu, University of Washington

Genetic overview

Genetic Background	Generation

Apbb1^tm1Quhu

Allele Type	Gene Symbol	Gene Name
Targeted (Null/Knockout)	Apbb1	amyloid beta (A4) precursor protein-binding, family B, member 1

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Research Applications

Neurobiology Research
Research Tools
Cell Biology Research

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Base Price

Starting at:

$2,854.50 Domestic price Cryo Recovery

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Details

Detailed Description

Homozygous mice are viable and normal in size and display no physical or histopathologically demonstrable abnormalities. Homozygotes are fertile but poor breeders, while heterozygous mice have no breeding problems. The endogenous full-length 97 kDa protein (p97) is not expressed in brain tissue from homozygous mice. The 60 kDa (p60) N-terminal truncated isoform of the endogenous protein is expressed in mutant and wildtype brain tissue, with mutant mice exhibiting 4-5-fold greater levels. Homozygous null mice exhibit slower learning rates on both aversive and spatial memory tasks and severe impairments in spatial memory extinction during relearning. Heterozygotes have an intermediate phenotype, except with normal spatial memory extinction during relearning. Fibroblasts from null mice show diminished neprilysin activity and mRNA expression. This mouse may be useful in studies of Alzheimer's disease, beta-amyloid precursor protein metabolism, hippocampus-dependent learning and memory, cell movement, transcription factors and activation, and cell cycle regulation.

Development

A targeting vector containing a phosphoglycerol kinase promoter driven neomycin resistance gene was inserted into exon 2 of the endogenous gene, replacing approximately 500 base pairs within the exon including the first three potential start codons. The construct was electroporated into (129X1/SvJ x 129S1/Sv)F1-derived R1 embryonic stem (ES) cells. Correctly targeted ES cells were injected into C57BL/6 blastocysts and the resulting chimeric males were bred to C57BL/6 females. Heterozygotes were backcrossed to C57BL/6J mice for more than 10 generations.

Control Suggestions

Wild-type from the colony
000664 C57BL/6J

Additional Information

Considerations for Choosing Controls

Selected References

Wang B; Hu Q; Hearn MG; Shimizu K; Ware CB; Liggitt DH; Jin LW; Cool BH; Storm DR; Martin GM. 2004. Isoform-specific knockout of FE65 leads to impaired learning and memory. J Neurosci Res 75(1):12-24PubMed: 14689444 MGI: J:94887

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Genetics

Apbb1^tm1Quhu

Allele Symbol: Apbb1^tm1Quhu

Allele Name	targeted mutation 1, Qubai Hu
Allele Type	Targeted (Null/Knockout)
Allele Synonym(s)	p97FE65^-
Gene Symbol and Name	Apbb1, amyloid beta (A4) precursor protein-binding, family B, member 1
Gene Synonym(s)
Strain of Origin	(129X1/SvJ x 129S1/Sv)F1-Kitl⁺
Chromosome	7
Molecular Note	A phosphoglycerate kinase (PGK) promoter-driven neomycin cassette replaced most of the exon 2 region. Northern and Western blot analysis as well as immunohistochemistry confirmed the absence of full-length (2.6 kB) transcription and 97kD translation products. However, the expression of a shorter 60kD isoform was retained in mutant mice, and this isoform appeared to be translated from an alternatively spliced trancript that did not contain exon 2. Western and GST pull-down analysis of brain lysates demonstrated that the expression of the 60kD isoform was increased 5-fold in mutant mice.
Mutations Made By	Qubai Hu, University of Washington

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
- Behavioral and Learning Defects
Research Tools
- Genetics Research
  - Mutagenesis and Transgenesis
  - Mutagenesis and Transgenesis: transcriptional activation
Cell Biology Research
- Cell Cycle Regulation
- Transcriptional Regulation

Mammalian Phenotype Terms by Genotype

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

Genotype: Apbb1^tm1Quhu/Apbb1⁺
involves: 129S1/Sv * 129X1/SvJ * C57BL/6

behavior/neurological phenotype

abnormal spatial learning
- e water-maze, in reversal learning, and normal locomotor activity in an open-field test
- 14 month old mutants showed an intermediate performance (worse than wild-type but better than homozygotes) in the hidden platform version of the Morris water-maze, but displayed normal learning and memory in the visible platform (nonspatial) version of the water-maze, in reversal learning, and normal locomotor activity in an open-field test

abnormal passive avoidance behavior
- at 14 months, impaired acquisition of passive avoidance learning (shorter step through latencies at days 2 and 3 after training than wild-type but longer than in homozygotes)

Genotype: Apbb1^tm1Quhu/Apbb1^tm1Quhu
involves: 129S1/Sv * 129X1/SvJ * C57BL/6

behavior/neurological phenotype

abnormal spatial learning
- displayed normal learning and memory in the visible platform (nonspatial) version of the water-maze and normal locomotor activity in an open-field test
- at 14 months, very poor performance in reversal spatial learning, indicating that mutants are deficient in extinction of old spatial references
- 14 month old mutants displayed impaired hippocampal-dependent spatial learning and memory tasks in the hidden platform (spatial) version of the Morris water-maze and in probe tests

abnormal passive avoidance behavior
- at 14 months, impaired acquisition of passive avoidance learning (shorter step through latencies at days 2 and 3 after training)

References

Wang B; Hu Q; Hearn MG; Shimizu K; Ware CB; Liggitt DH; Jin LW; Cool BH; Storm DR; Martin GM. 2004. Isoform-specific knockout of FE65 leads to impaired learning and memory. J Neurosci Res 75(1):12-24PubMed: 14689444 MGI: J:94887

Additional - Apbb1^tm1Quhu related

Technical Support

CONTACT TECHNICAL SUPPORT

Genotyping Protocols
- Standard PCR:Apbb1
- Genotyping resources and troubleshooting
Breeding Considerations

When maintaining a live colony, these mice are bred as heterozygotes. Homozygous null mice are fertile but poor breeders.
- Additional Breeding and Husbandry Support
Citation
When using the p97FE65 KO mouse strain in a publication, please cite the originating article(s) and include JAX stock #005708 in your Materials and Methods section.

Animal Health Reports

Facility Barrier Level Descriptions

Production of mice from cryopreserved embryos or sperm occurs in a maximum barrier room, G200

Pricing & Availability

Cryo Recovery

Domestic
International

Live Mouse

Age

Genotype

Price

weeks

Cryorecovery - Pricing

Service/Product	Description	Price
	Heterozygous or Wild-type for Apbb1<tm1Quhu>

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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. We do not guarantee breeding performance and therefore suggest that investigators order more than one breeding pair to avoid delays in their research.

Terms Of Use

General Terms and Conditions

Questions about Terms of Use

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Licensing Information

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Also Known As:p97FE65 KO

Donating Investigator

Genetic overview

Research Applications

Base Price

Detailed Description

Development

Control Suggestions

Additional Information

Selected References

Apbb1tm1Quhu

Allele Symbol: Apbb1tm1Quhu

Disease Terms

Research Areas By Phenotype

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

Mammalian Phenotype Terms by Genotype

Genotype: Apbb1tm1Quhu/Apbb1+involves: 129S1/Sv * 129X1/SvJ * C57BL/6

behavior/neurological phenotype

Genotype: Apbb1tm1Quhu/Apbb1tm1Quhuinvolves: 129S1/Sv * 129X1/SvJ * C57BL/6

behavior/neurological phenotype

References

Additional - Apbb1tm1Quhu related

Genotyping Protocols

Breeding Considerations

Citation

Animal Health Reports

Production of mice from cryopreserved embryos or sperm occurs in a maximum barrier room, G200

Live Mouse

Cryorecovery - 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

Apbb1^tm1Quhu

Allele Symbol: Apbb1^tm1Quhu

Genotype: Apbb1^tm1Quhu/Apbb1⁺
involves: 129S1/Sv * 129X1/SvJ * C57BL/6

Genotype: Apbb1^tm1Quhu/Apbb1^tm1Quhu
involves: 129S1/Sv * 129X1/SvJ * C57BL/6

Additional - Apbb1^tm1Quhu related