Description

Strain Information

Type Congenic; Mutant Strain; Transgenic; Additional information on Genetically Engineered and Mutant Mice. Visit our online Nomenclature tutorial. Additional information on Congenic nomenclature. Mating System Hemizygote x Inbred         (Female x Male)   01-MAR-06 Species laboratory mouse Generation N11+13 (24-DEC-08)   Donating Investigator Lennart Mucke,   Gladstone Inst of Neurological Disease

Description
These transgenic mice express a wildtype human amyloid protein precursor (APP) under the control of the human platelet-derived growth factor beta polypeptide (PDGFB) promoter. PCR primer modification was used to alter the sequence of the APPInd mutation to the wildtype sequence in this transgene. Hemizygotes express immunodetectable transgene product in cerebral neurons, with the highest level of expression occurring in the neocortex and hippocampus. Enzyme-linked immunosorbent assay (ELISA) analysis of neocortical and hippocampal tissue reveals approximate total amyloid beta peptides levels and 42 amino acid length amyloid beta peptides levels that are lower than levels found in the APP SwInd mutant line. No amyloid plaques are detected by immunohistochemistry at 8-10 months of age or at 24 months of age. Mutants display age dependent decrease in density of synaptophysin-immunoreactive presynaptic terminals indicative of neurodegeneration. This strain serves as the control for Stock No. 006293.

Development
The APPInd transgene sequence was changed using PCR primer modification to the wildtype sequence. The transgenic construct containing the reverted wildtype human amyloid protein precursor, APP, under the control of human platelet-derived growth factor beta polypeptide, simian sarcoma viral (v-sis) oncogene homolog, (PDGFB) promoter, was injected into C57BL/6 X DBA/2 F2 one-cell embryos. Heterozygous founder animals were bred to C57BL/6 X DBA/2 F1 mice.

Control Information

		This strain serves as a control for Stock No. 006293.
Considerations for Choosing Controls

Related Strains

Strains carrying other alleles of APP

008609	129S1.129(Cg)-Tg(APPSw)40Btla/2J
006409	129S1.129(Cg)-Tg(APPSw)40Btla/J
006555	A.129(B6)-Tg(APPSw)40Btla/J
005300	B6.129-Tg(APPSw)40Btla/J
005301	B6.129S2-Tg(APP)8.9Btla/J
006406	B6.129S4-Tg(APPSwLon)96Btla/J
009126	B6.Cg-Nos2tm1Lau Tg(Thy1-APPSwDutIowa)BWevn/J
005864	B6.Cg-Tg(APPswe,PSEN1dE9)85Dbo/J
006293	B6.Cg-Tg(PDGFB-APPSwInd)20Lms/2J
006006	B6.Cg-Tg(Prnp-APP)A-2Dbo/J
006005	B6.Cg-Tg(Prnp-App/APPswe)E1-2Dbo/J
007049	B6.Cg-Tg(tetO-APPSwInd)885Dbo/J
004462	B6C3-Tg(APPswe,PSEN1dE9)85Dbo/J
006004	B6C3-Tg(tetO-APPSwInd)885Dbo/J
007027	C57BL/6-Tg(Thy1-APPSwDutIowa)BWevn/J
006472	D2.129(B6)-Tg(APPSw)40Btla/J

View Strains carrying other alleles of APP     (16 strains)

Strains carrying other alleles of PDGFB

006293

B6.Cg-Tg(PDGFB-APPSwInd)20Lms/2J

View Strains carrying other alleles of PDGFB     (1 strain)

Additional Web Information

JAX^® NOTES, Summer 2004; 494. New Mouse Models for Alzheimer's Disease Research.
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.

Tg(PDGFB-APP)5Lms/?

        involves: C57BL/6 * DBA/2

• nervous system phenotype
• *normal* nervous system phenotype (MGI Ref ID J:62290)
  • no amyloid plaques are detected by immunohistochemistry up to the age of 24 months
• amyloid beta deposits (MGI Ref ID J:137264)
  • significantly elevated beta amyloid
  • a further 3 fold increase in amyloid beta 40 but not amyloid beta 42 when placed on a high fat diet
• neurodegeneration (MGI Ref ID J:62290)
  • neurodegeneration is indicated by an age dependent decrease in density of synaptophysin-immunoreactive presynaptic terminals
• other phenotype
• amyloid beta deposits (MGI Ref ID J:137264)
  • significantly elevated beta amyloid
  • a further 3 fold increase in amyloid beta 40 but not amyloid beta 42 when placed on a high fat diet

View Research Applications

Research Applications

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

APP related

Mouse/Human Gene Homologs
Alzheimer's

Neurobiology Research
Neurodegeneration

Tg(PDGFB-APP)5Lms related

Neurobiology Research
Alzheimer's Disease

Genes & Alleles

Gene & Allele Information

Allele Symbol		Tg(PDGFB-APP)5Lms
Allele Name		transgene insertion 5, Lennart Mucke
Allele Type		Transgenic (random, expressed)
Common Name(s)		I5; PDGF-APPWT; hAPPWT; line I5;
Mutation Made By		Lennart Mucke,   Gladstone Inst of Neurological Disease
Strain of Origin		(C57BL/6 x DBA/2)F2
Expressed Gene		APP, amyloid beta (A4) precursor protein, human
Promoter		PDGFB, platelet-derived growth factor beta polypeptide (simian sarcoma viral (v-sis) oncogene homolog), human
Molecular Note		The transgene contains the reverted wild-type human amyloid protein precursor, APP, under the control of the human platelet derived growth factor, B polypeptide, (PDGFB) promoter. Hemizygous transgenic mice express immunodetectable transgene product in cerebral neurons, with the highest level of expression occurring in the neocortex and hippocampus. ELISA analysis of neocortical and hippocampal tissue revealed approximate total amyloid beta peptides levels and 42 amino acid length amyloid beta peptides levels that were lower than levels found in mice carrying the mutant human amyloid protein precursor transgene Tg(PDGFB-APPSwInd)20Lms. [MGI Ref ID J:62290]

Genotyping

Genotyping Information

Genotyping Protocols

Tg(PDGFB-APP), Melt Curve Analysis
Tg(PDGFB-APP), Melt Curve Analysis
Tg(PDGFB-APP), Standard PCR

Helpful Links

Genotyping resources and troubleshooting

References

References

Selected Reference(s)

Mucke L; Masliah E; Yu GQ; Mallory M; Rockenstein EM; Tatsuno G; Hu K; Kholodenko D; Johnson-Wood K; McConlogue L. 2000. High-level neuronal expression of abeta 1-42 in wild-type human amyloid protein precursor transgenic mice: synaptotoxicity without plaque formation. J Neurosci 20(11):4050-8. [PubMed: 10818140]  [MGI Ref ID J:62290]

Additional References

Tg(PDGFB-APP)5Lms related

Chin J; Massaro CM; Palop JJ; Thwin MT; Yu GQ; Bien-Ly N; Bender A; Mucke L. 2007. Reelin depletion in the Enthorhinal cortex of human amyloid precursor protein transgenic mice and humans with Alzheimer's disease J Neurosci 27(11):2727-2733. [PubMed: 17360894]  [MGI Ref ID J:118589]

Ho RC; Fujii N; Witters LA; Hirshman MF; Goodyear LJ. 2007. Dissociation of AMP-activated protein kinase and p38 mitogen-activated protein kinase signaling in skeletal muscle. Biochem Biophys Res Commun 362(2):354-9. [PubMed: 17709097]  [MGI Ref ID J:125174]

Hook VY; Kindy M; Reinheckel T; Peters C; Hook G. 2009. Genetic cathepsin B deficiency reduces beta-amyloid in transgenic mice expressing human wild-type amyloid precursor protein. Biochem Biophys Res Commun 386(2):284-8. [PubMed: 19501042]  [MGI Ref ID J:151423]

Palop JJ; Chin J; Roberson ED; Wang J; Thwin MT; Bien-Ly N; Yoo J; Ho KO; Yu GQ; Kreitzer A; Finkbeiner S; Noebels JL; Mucke L. 2007. Aberrant excitatory neuronal activity and compensatory remodeling of inhibitory hippocampal circuits in mouse models of Alzheimer's disease. Neuron 55(5):697-711. [PubMed: 17785178]  [MGI Ref ID J:126808]

Seeger G; Gartner U; Ueberham U; Rohn S; Arendt T. 2009. FAD-mutation of APP is associated with a loss of its synaptotrophic activity. Neurobiol Dis 35(2):258-63. [PubMed: 19450683]  [MGI Ref ID J:150433]

Simon AM; Schiapparelli L; Salazar-Colocho P; Cuadrado-Tejedor M; Escribano L; Lopez de Maturana R; Del Rio J; Perez-Mediavilla A; Frechilla D. 2009. Overexpression of wild-type human APP in mice causes cognitive deficits and pathological features unrelated to Abeta levels. Neurobiol Dis 33(3):369-78. [PubMed: 19101630]  [MGI Ref ID J:146301]

Thirumangalakudi L; Prakasam A; Zhang R; Bimonte-Nelson H; Sambamurti K; Kindy MS; Bhat NR. 2008. High cholesterol-induced neuroinflammation and amyloid precursor protein processing correlate with loss of working memory in mice. J Neurochem 106(1):475-85. [PubMed: 18410513]  [MGI Ref ID J:137264]

Health & husbandry

Health & Colony Maintenance Information

Animal Health Reports

Room Number           AX12

Colony Maintenance

Mating System	Hemizygote x Inbred         (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

		This strain serves as a control for Stock No. 006293.
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.

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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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