Due to low transgenic copy number and consequent delayed onset of phenotype, this strain has been re-imported from the Mucke lab with a new stock number. Please see Stock No. 006293.
Lennart Mucke, Gladstone Inst of Neurological Disease
Genetic Background | Generation |
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Allele Type |
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Transgenic (Inserted expressed sequence, Humanized sequence) |
THIS STRAIN HAS BEEN FOUND TO HAVE LOW COPY NUMBER OF THE TRANSGENE AND CONSEQUENT LOSS OR DELAYED ONSET OF PHENOTYPE. THIS STRAIN IS NO LONGER AVAILABLE, AND HAS BEEN REPLACED BY THE RE-IMPORTED LINE, SEE: STOCK NO. 006293.
These transgenic mice express a mutant form of the human amyloid protein precursor bearing both the Swedish (K670N/M671L) and the Indiana (V717F) mutations (APPSwInd). Expression of the transgenic insert is directed by the human platelet-derived growth factor beta polypeptide (PDGFB) promoter. 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 reveals approximate total amyloid beta peptides and 42 amino acid length amyloid beta peptides in neocortical and hippocampal tissue from mutant mice. At 5 to 7 months of age diffuse amyloid beta peptides deposition in the dendate gyrus and neocortex forms. Amyloid deposition is progressive with all transgenic mice exhibiting plaques by age 8 to 10 months. This mutant mouse strain represents a model that may be useful in studies of the pathogenesis of Familial Alzheimer's Disease and possible therapeutic treatments.
A transgenic construct containing the mutant human amyloid protein precursor APPSwInd 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.
Expressed Gene | APP, amyloid beta precursor protein, human |
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Site of Expression | APPSwInd is expressed in cerebral neurons, with the highest level in the neocortex and hippocampus. |
Allele Name | transgene insertion 20, Lennart Mucke |
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Allele Type | Transgenic (Inserted expressed sequence, Humanized sequence) |
Allele Synonym(s) | APP Tg; APP/J20; hAPPJ20; hAPP-J20; J20; PDAPP-J20; PDGF-APPSwInd; PDGF-hAPP695,751,770V171F, KM670/671NL; Tg(PDGFB-APP*Swe*Ind)20Lms |
Gene Symbol and Name | Zbtb20, zinc finger and BTB domain containing 20 |
Gene Synonym(s) | |
Promoter | PDGFB, platelet derived growth factor subunit B, human |
Expressed Gene | APP, amyloid beta precursor protein, human |
Site of Expression | APPSwInd is expressed in cerebral neurons, with the highest level in the neocortex and hippocampus. |
Strain of Origin | (C57BL/6 x DBA/2)F2 |
Chromosome | 16 |
General Note | This line is also called line J20. Diffuse amyloid beta peptides deposition forms in the dendate gyrus and neocortex at 5 to 7 months of age. Amyloid deposition is progressive, with all transgenic mice exhibiting plaques by age 8 to 10 months. |
Molecular Note | The transgene expresses the mutant human amyloid protein precursor APPSwInd, which bears both the Swedish (K670N/M671L) and the Indiana (V717F) mutations, 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 reveals approximate total amyloid beta peptides and 42 amino acid length amyloid beta peptides in neocortical and hippocampal tissue from transgenic mice. Line 20 inserted into an intron of the gene at 43086322-43127049 (Build GRCm38/mm10) resulting in a 40,727 bp deletion. Founder line 20 has a copy number of greater than 10. |
Mutations Made By | Lennart Mucke, Gladstone Inst of Neurological Disease |
The resulting transgenic mice were then backcrossed for 12 generations on the C57BL/6J background. The strain is maintained as a hemizygote. Expected coat color is black.
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