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.
Qubai Hu, University of Washington
Genetic Background | Generation |
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|
Allele Type | Gene Symbol | Gene Name |
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Targeted (Null/Knockout) | Apbb1 | amyloid beta (A4) precursor protein-binding, family B, member 1 |
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.
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.
Allele Name | targeted mutation 1, Qubai Hu |
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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 |
When maintaining a live colony, these mice are bred as heterozygotes. Homozygous null mice are fertile but poor breeders.
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.
Facility Barrier Level Descriptions
Service/Product | Description | Price |
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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.
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