Description

The genotypes of the animals provided may not reflect those discussed in the strain description or the mating scheme utilized by The Jackson Laboratory prior to cryopreservation. Please inquire for possible genotypes for this specific strain.

Strain Information

Type Congenic; Mutant Strain; Targeted Mutation; Additional information on Genetically Engineered and Mutant Mice. Visit our online Nomenclature tutorial. Additional information on Congenic nomenclature. Species laboratory mouse Generation N11p (19-FEB-06)   Donating Investigator Qubai Hu,   University of Washington

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 Information

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

Additional Web Information

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

Phenotype

Phenotype Information

View Mammalian Phenotype Terms

Mammalian Phenotype Terms

      assigned by genotype

The following phenotype information may relate to a genetic background differing from this JAX^® Mice strain.

Apbb1^tm1Quhu/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

Apbb1^tm1Quhu/Apbb1^tm1Quhu

        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

View Research Applications

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

Genes & Alleles

Gene & Allele Information

Allele Symbol		Apbb1tm1Quhu
Allele Name		targeted mutation 1, Qubai Hu
Allele Type		Targeted (knock-out)
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]

Genotyping

Genotyping Information

Genotyping Protocols

Apbb1^tm1Quhu, Standard PCR

Helpful Links

Genotyping resources and troubleshooting

References

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

Apbb1^tm1Quhu related

Ma QH; Futagawa T; Yang WL; Jiang XD; Zeng L; Takeda Y; Xu RX; Bagnard D; Schachner M; Furley AJ; Karagogeos D; Watanabe K; Dawe GS; Xiao ZC. 2008. A TAG1-APP signalling pathway through Fe65 negatively modulates neurogenesis. Nat Cell Biol 10(3):283-94. [PubMed: 18278038]  [MGI Ref ID J:145671]

Pardossi-Piquard R; Petit A; Kawarai T; Sunyach C; Alves da Costa C; Vincent B; Ring S; D'Adamio L; Shen J; Muller U; St George Hyslop P; Checler F. 2005. Presenilin-dependent transcriptional control of the Abeta-degrading enzyme neprilysin by intracellular domains of betaAPP and APLP. Neuron 46(4):541-54. [PubMed: 15944124]  [MGI Ref ID J:100260]

Health & husbandry

The genotypes of the animals provided may not reflect those discussed in the strain description or the mating scheme utilized by The Jackson Laboratory prior to cryopreservation. Please inquire for possible genotypes for this specific strain.

Health & Colony Maintenance Information

Colony Maintenance

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

Purchasing information

Pricing, Supply Level & Notes, Controls, General Terms & Conditions

Pricing

Supply Details

Standard Supply

Cryopreserved. Ready for recovery. Please refer to pricing and supply notes for further information.

Supply Notes

Cryorecovery - Standard. We will fulfill your order by providing at least two pair of mice, at least one animal of each pair carrying the mutation of interest. The total number of animals provided, their gender and genotype will vary. Please inquire if larger numbers of animals with specific genotype and genders are needed. Animals typically ship between 13 and 16 weeks from the date of your order. If a second cryorecovery is needed in order to provide the minimum number of animals, animals will ship within 25 weeks. IMPORTANT NOTE: The genotypes of animals provided may not reflect the mating scheme utilized by The Jackson Laboratory prior to cryopreservation, or that discussed in the strain description. Please inquire about possible genotypes which will be recovered for this specific strain. The Jackson Laboratory 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. For more information on Dedicated Supply, please contact JAX® Services, Tel: 1-800-422-6423 (from U.S.A., Canada or Puerto Rico only) or 1-207-288-5845 (from any location). This strain is included in the Induced Mutant Resource Colony collection.

Control Information

	Control
	Wild-type from the colony
	000664 C57BL/6J
Considerations for Choosing Controls
USA, Canada and Mexico - Control Pricing Information for Genetically Engineered Mutant Strains.
International - Control Pricing Information for Genetically Engineered Mutant Strains.

Payment Terms and Conditions

Terms are granted by individual review and stated on the customer invoice(s) and account statement. These transactions are payable in U.S. currency within the granted terms. Payment for services, products, shipping containers, and shipping costs that are rendered are expected within the payment terms indicated on the invoice or stated by contract. Invoices and account balances in arrears of stated terms may result in The Jackson Laboratory pursuing collection activities including but not limited to outside agencies and court filings.

See Terms of Use tab for General Terms and Conditions

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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Terms of Use

Terms of Use

General Terms and Conditions

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Contact information

General inquiries

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phone:	207-288-6470
fax:	207-288-6655

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