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Genes & Alleles

Apbb1;   Apbb1tm1Quhu;

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Product Information

Strain Details

Type JAX® GEMM® Strain - Congenic Additional information on JAX® GEMM® Strains. Type JAX® GEMM® Strain - Mutant Strain Type JAX® GEMM® Strain - Targeted Mutation Species laboratory mouse Donating Investigator Qubai Hu,   University of Washington

Strain 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.

Strain 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.

Mammalian Phenotype Terms assigned by genotype The following phenotype information may relate to a genetic background differing from this JAX® Mice strain. Apbb1tm1Quhu/Apbb1+         involves: 129S1/Sv * 129X1/SvJ * C57BL/6 behavior/neurological phenotype abnormal passive avoidance behavior (MGI Ref ID J:94887) 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) abnormal spatial learning (MGI Ref ID J:94887) 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 Apbb1tm1Quhu/Apbb1tm1Quhu         involves: 129S1/Sv * 129X1/SvJ * C57BL/6 behavior/neurological phenotype abnormal passive avoidance behavior (MGI Ref ID J:94887) at 14 months, impaired acquisition of passive avoidance learning (shorter step through latencies at days 2 and 3 after training) abnormal spatial learning (MGI Ref ID J:94887) 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 at 14 months, very poor performance in reversal spatial learning, indicating that mutants are deficient in extinction of old spatial references displayed normal learning and memory in the visible platform (nonspatial) version of the water-maze and normal locomotor activity in an open-field test

Gene & Allele Details

Allele Symbol		Apbb1tm1Quhu
Allele Name		targeted mutation 1, Qubai Hu
Common Name(s)		p97FE65-;
Mutation Made By		Qubai Hu,   University of Washington
Strain of Origin		(129X1/SvJ x 129S1/Sv)F1-Kitl+
ES Cell Line Name		R1
ES Cell Line Strain		(129X1/SvJ x 129S1/Sv)F1-Kitl<+>
Gene Symbol and Name		Apbb1, amyloid beta (A4) precursor protein-binding, family B, member 1
Chromosome		7
Gene Common Name(s)		FE65; MGC:9072; RIR; Rir; retroviral integrase related;
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. [MGI Ref ID J:94887]

Control Information

	Control
	Wild-type from the colony
	000664 C57BL/6J
Considerations for Choosing Controls

Genotyping Protocols

Apbb1^tm1Quhu

Colony Maintenance

Breeding & Husbandry	When maintaining a live colony, these mice are bred as heterozygotes. Homozygous null mice are fertile but poor breeders.

Additional Web Information

Congenic Nomenclature
Visit the Alzheimer's Disease Mouse Model Resource site for helpful information on Alzheimer's Disease and research resources.

Research Applications

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

Cell Biology Research
Cell Cycle Regulation
Transcriptional Regulation

Neurobiology Research
Alzheimer's Disease
Behavioral and Learning Defects

Research Tools
Genetics Research (Mutagenesis and Transgenesis: transcriptional activation)

References

Selected Reference(s)

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):12-24. [PubMed: 14689444]  [MGI Ref ID J:94887]

Additional References

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Price and Supply Information

Strain Name:	B6.129-Apbb1tm1Quhu/J
Stock Number:	005708

Price Details

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Supply Details

Standard Supply	Repository-Cryopreserved. Must Be Recovered. Please refer to pricing and supply notes for further information.
Supply Notes	Cryorecovery - Standard. The recovery process begins when a signed agreement form is returned to the Customer Service Department after order placement. Although results vary by strain, at least two males and two females (two pairs) will be provided, typically within 15 weeks of our receipt of the signed agreement form. If the first recovery attempt is unsuccessful or only one pair is recovered, a second recovery will be done, extending the delivery time to approximately 25 weeks. At least one member of each pair will be of known genotype and will carry the mutation if it is a mutant strain. Please note that pairs may not reflect the mating scheme utilized by The Jackson Laboratory prior to cryopreservation of the strain. Mating schemes are sometimes modified for successful cryopreservation. Price represents a repository maintenance fee, which includes the cost of recovery of the strain from the cryopreservation resource and the periodic replacement of the frozen embryos used for recovery. Cryorecovery to establish a Dedicated Supply for greater quantities of mice. One to two pairs will be recovered to establish a Dedicated Supply of mice. Price by quotation. For more information on Dedicated Supply, please contact JAX® Services: Tel: 1-800-422-6423 or 1-207-288-5845; Email: jaxservices@jax.org. This strain is included in the Induced Mutant Resource Colony collection.
Licensing	See General Terms and Conditions below for Licensing and Use Restrictions
Control Information	View Control Information in Strain Details.

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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.

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