B6.129-Apbb1^tm1Quhu/J

Stock number: 005708
Product name: p97FE65 KO
Research areas: Cell Biology Research, Neurobiology Research, Research Tools

Description

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.

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.

Allele

Symbol: Apbb1^tm1Quhu
Name: targeted mutation 1, Qubai Hu
MGI accession ID: MGI:3514266
Generation method: Targeted
Attributes: Null/Knockout
Marker symbol: Apbb1
Marker name: amyloid beta (A4) precursor protein-binding, family B, member 1
Chromosome: 7
Strain of origin: (129X1/SvJ x 129S1/Sv)F1-Kitl⁺
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.