Description

Strain Information

Former Names B6.129-Bacetm1Pcw/J    (Changed: 15-DEC-04 ) Type Mutant Strain; Targeted Mutation; Additional information on Genetically Engineered and Mutant Mice. Visit our online Nomenclature tutorial. Mating System Homozygote x Homozygote         (Female x Male)   01-MAR-06 Species laboratory mouse Generation N7F?+N1F7+N1F1 (18-MAY-09)   Donating Investigator Philip Wong,   Johns Hopkins University

Description
Mice that are homozygous for the targeted mutation are viable, fertile, normal in size and do not display any gross physical or behavioral abnormalities. No gene product (protein) is detected by Western blot analysis of brain tissue. Primary cultures of cortical neurons isolated from homozygotes aged embryonic day 16.5 do not secrete amyloid beta peptides (Aβ1-40/42 or Aβ11-40/42) or beta C-terminal fragments (βCTFs). When transfected with a recombinant adenovirus expressing the mutant humanized Beta amyloid precursor protein (APP), hAPPSwe, cultured embryonic cortical neurons do not secrete detectable levels of Aβ1-40/42 or Aβ11-40/42 peptides. This mutant mouse strain may be useful in studies of Alzheimer's disease.

Development
A targeting vector containing neomycin resistance and herpes simplex virus thymidine kinase genes was used to disrupt 2kb of sequence containing exon 1 of the targeted gene. The construct was electroporated into 129-derived R1 embryonic stem (ES) cells. Correctly targeted ES cells were injected into C57BL/6J blastocysts.

Control Information

	Control
	000664 C57BL/6J
Considerations for Choosing Controls

Additional Web Information

Genetic Quality Control Annual Report
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.

Bace1^tm1Pcw/Bace1^tm1Pcw

        involves: 129S1/Sv * 129X1/SvJ * C57BL/6J

• behavior/neurological phenotype
• abnormal locomotor activation (MGI Ref ID J:123534)
  • swimming speed is lower than controls in Morris water maze
• abnormal spatial learning (MGI Ref ID J:123534)
• abnormal spatial reference memory (MGI Ref ID J:123534)
  • in Morris water maze, 3-month old mice show normal learning and memory for location of hidden platform, but at 16 months, mutant animals display significantly impaired spatial reference memory during probe trials compared to normal or heterozygous littermates, while performance in hidden platform trials is not significantly different
• abnormal spatial working memory (MGI Ref ID J:123534)
  • in spatial working memory tasks using the radial arm water maze, mice are significantly impaired compared to littermates; deficit is observed in Y-maze task, with mutant animals showing deficits in arm alternation
• decreased anxiety-related response (MGI Ref ID J:123534)
  • in an open-field task, mice display low anxiety-type behavior like greater distance traveled and more frequent and active visits to open center of field compared to control heterozygotes and wild-type mice
• nervous system phenotype
• abnormal long term depression (MGI Ref ID J:123534)
  • after LTD saturation, mice display a larger de-depression than controls
• enhanced paired-pulse facilitation (MGI Ref ID J:123534)
  • the PPF ratio is significantly increased at short interstimulus intervals (ISIs) relative to controls, but not at long ISIs

Bace1^tm1Pcw/Bace1^tm1Pcw

        involves: 129S1/Sv * 129X1/SvJ

• behavior/neurological phenotype
• abnormal grip strength (MGI Ref ID J:116162)
  • mice show reduced grip strength (1.13) relative to wild-type controls (1.26)
• decreased thermal nociceptive threshold (MGI Ref ID J:116162)
  • mutants retract paws from thermal stimulus more rapidly than wild-type controls, indicating greater pain sensitivity
• nervous system phenotype
• abnormal myelin sheath morphology (MGI Ref ID J:116162)
  • in 2-month old mice, myelin sheaths are significantly thinner in optic nerves compared to wild-type controls
  • more axons in sciatic nerve of mutants appear smaller in diameter than in wild-type
• abnormal myelination (MGI Ref ID J:116162)
  • hypomyelination is observed in hippocampus and cerebral cortex at P15 and P30, but axonal development is normal
  • sciatic nerve is hypomyelinated in mutants
• touch/vibrissae phenotype
• decreased thermal nociceptive threshold (MGI Ref ID J:116162)
  • mutants retract paws from thermal stimulus more rapidly than wild-type controls, indicating greater pain sensitivity

View Research Applications

Research Applications

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

Mouse/Human Gene Homologs
Alzheimer's

Neurobiology Research
Alzheimer's Disease
      Bace mutants

Bace1^tm1Pcw related

Neurobiology Research
Alzheimer's Disease

Genes & Alleles

Gene & Allele Information

Allele Symbol		Bace1tm1Pcw
Allele Name		targeted mutation 1, Philip C Wong
Allele Type		Targeted (knock-out)
Common Name(s)		BACE1-;
Mutation Made By		Philip Wong,   Johns Hopkins University
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		Bace1, beta-site APP cleaving enzyme 1
Chromosome		9
Gene Common Name(s)		ASP2; BACE; C76936; FLJ90568; HSPC104; KIAA1149; expressed sequence C76936;
Molecular Note		Exon 1 was replaced with a neomycin selection cassette inserted by homologous recombination. Normal protein was undetected by Western blot analysis of homozygous mutant embryos. [MGI Ref ID J:79847]

Genotyping

Genotyping Information

Genotyping Protocols

Bace^tm1Pcw, Melt Curve Analysis
Bace1^tm1Pcw, Standard PCR

Helpful Links

Genotyping resources and troubleshooting

References

References

Selected Reference(s)

Cai H; Wang Y; McCarthy D; Wen H; Borchelt DR; Price DL; Wong PC. 2001. BACE1 is the major beta-secretase for generation of Abeta peptides by neurons. Nat Neurosci 4(3):233-4. [PubMed: 11224536]  [MGI Ref ID J:79847]

Additional References

Bace1^tm1Pcw related

Hu X; He W; Diaconu C; Tang X; Kidd GJ; Macklin WB; Trapp BD; Yan R. 2008. Genetic deletion of BACE1 in mice affects remyelination of sciatic nerves. FASEB J 22(8):2970-80. [PubMed: 18413858]  [MGI Ref ID J:137970]

Hu X; Hicks CW; He W; Wong P; Macklin WB; Trapp BD; Yan R. 2006. Bace1 modulates myelination in the central and peripheral nervous system. Nat Neurosci 9(12):1520-5. [PubMed: 17099708]  [MGI Ref ID J:116162]

Laird FM; Cai H; Savonenko AV; Farah MH; He K; Melnikova T; Wen H; Chiang HC; Xu G; Koliatsos VE; Borchelt DR; Price DL; Lee HK; Wong PC. 2005. BACE1, a major determinant of selective vulnerability of the brain to amyloid-beta amyloidogenesis, is essential for cognitive, emotional, and synaptic functions. J Neurosci 25(50):11693-709. [PubMed: 16354928]  [MGI Ref ID J:123534]

Liang X; Wang Q; Hand T; Wu L; Breyer RM; Montine TJ; Andreasson K. 2005. Deletion of the prostaglandin E2 EP2 receptor reduces oxidative damage and amyloid burden in a model of Alzheimer's disease. J Neurosci 25(44):10180-7. [PubMed: 16267225]  [MGI Ref ID J:102728]

Loane DJ; Pocivavsek A; Moussa CE; Thompson R; Matsuoka Y; Faden AI; Rebeck GW; Burns MP. 2009. Amyloid precursor protein secretases as therapeutic targets for traumatic brain injury. Nat Med 15(4):377-9. [PubMed: 19287391]  [MGI Ref ID J:149374]

Philipson O; Lannfelt L; Nilsson LN. 2009. Genetic and pharmacological evidence of intraneuronal Abeta accumulation in APP transgenic mice. FEBS Lett 583(18):3021-6. [PubMed: 19683527]  [MGI Ref ID J:152969]

Savonenko AV; Melnikova T; Laird FM; Stewart KA; Price DL; Wong PC. 2008. Alteration of BACE1-dependent NRG1/ErbB4 signaling and schizophrenia-like phenotypes in BACE1-null mice. Proc Natl Acad Sci U S A 105(14):5585-90. [PubMed: 18385378]  [MGI Ref ID J:133643]

Varvel NH; Bhaskar K; Patil AR; Pimplikar SW; Herrup K; Lamb BT. 2008. Abeta oligomers induce neuronal cell cycle events in Alzheimer's disease. J Neurosci 28(43):10786-93. [PubMed: 18945886]  [MGI Ref ID J:144634]

Wang H; Song L; Laird F; Wong PC; Lee HK. 2008. BACE1 knock-outs display deficits in activity-dependent potentiation of synaptic transmission at mossy fiber to CA3 synapses in the hippocampus. J Neurosci 28(35):8677-81. [PubMed: 18753368]  [MGI Ref ID J:138795]

Health & husbandry

Health & Colony Maintenance Information

Animal Health Reports

Room Number           AX12

Colony Maintenance

Breeding & Husbandry	The resulting chimeric animals were crossed to C57BL/6 mice, and then backcrossed to the same for 7 generations. The strain is currently maintained as a homozygote.
Mating System	Homozygote x Homozygote         (Female x Male)   01-MAR-06
Diet Information	LabDiet® 5K52/5K67

Purchasing information

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

Pricing

Supply Details

Standard Supply

Repository-Live. A collection of over 1000 strains maintained as live colonies. Individual colonies are sized to meet current customer demand. Delivery for orders of 10 mice or less ranges on average from one to eight weeks; mice are generally shipped between four to six weeks of age with a maximum shipping age of approximately nine weeks. Colony sizes do not generally support stringent age specifications for large volumes of mice; however custom orders and larger quantities of mice are easily arranged. Estimated ship dates for all orders provided within two business days following order placement.

Supply Notes

Usually shipped between four and eight weeks of age. This strain is included in the Induced Mutant Resource Colony collection. Genomic DNA is available for this strain from the Mouse DNA Resource.

Control Information

	Control
	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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Ordering and Purchasing Information

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Contact Information
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Fax: 1-207-288-6150
Technical Support Email Form

Terms of Use

Terms of Use

General Terms and Conditions

For Licensing and Use Restrictions view the link(s) below:
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Contact information

General inquiries

Contracts Administration

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

JAX^® Mice, Products & Services Conditions of Use

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