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Strain Name:

B6.129-Bace1tm1Pcw/J

Stock Number:

004714

Availability:

Repository- Live

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Former Name      B6.129-Bacetm1Pcw/J    (Changed: 15-DEC-04 )
Genes & Alleles   Bace1;   Bace1tm1Pcw;

Product Information

Strain Details

Type JAX® GEMM® Strain - Mutant Strain
Additional information on JAX® GEMM® Strains.
Type JAX® GEMM® Strain - Targeted Mutation
Mating SystemHomozygote x Homozygote         (Female x Male)
Specieslaboratory mouse
Donating Investigator Philip Wong,   Johns Hopkins University
GenerationN7F?+N1F7 (05-DEC-07)

Strain 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.

Strain 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.

Mammalian Phenotype Terms assigned by genotype

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

Bace1tm1Pcw/Bace1tm1Pcw

        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
  • decreased paired-pulse facilitation (MGI Ref ID J:123534)
    • PPF ratio is significantly increased relative to controls

Bace1tm1Pcw/Bace1tm1Pcw

        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

Gene & Allele Details

Allele Symbol Bace1tm1Pcw
Allele Name targeted mutation 1, Philip C Wong
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 NameR1
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]

Control Information

  Control
   000664 C57BL/6J
 
  Considerations for Choosing Controls

Genotyping Protocols

Bace1tm1Pcw

Colony Maintenance

Breeding & HusbandryThe 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.
Diet Information LabDiet® 5K52/5K67

Additional Web Information

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

Animal Health Reports

Room Number           AX12

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)

Bace1tm1Pcw related

Neurobiology Research
Alzheimer's Disease

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

Price and Supply Information

Strain Name: B6.129-Bace1tm1Pcw/J
Stock Number: 004714

Price Details

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Supply Details

Standard SupplyRepository-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 ~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 48 hours of 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.
LicensingSee General Terms and Conditions below for Licensing and Use Restrictions  
Control InformationView Control Information in Strain Details.

General Terms and Conditions

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- Use of MICE by companies or for-profit entities requires a license prior to shipping.

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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.
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