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). They show progressive amyloid deposition as they age. 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.
Lennart Mucke, Gladstone Inst of Neurological Disease
Genetic Background | Generation |
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N12+N30
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Allele Type |
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Transgenic (Inserted expressed sequence, Humanized sequence) |
In March 2010, the donating investigator performed quantitative PCR on genomic DNA and determination of amyloid-beta levels in brain extract from the JAX Stock No. 006293 distribution colony (B6.Cg-Tg(PDGFB-APPSwInd)20Lms/2J also called "J20" line). Results of these analyses demonstrate that the current distribution colony maintains similar transgene copy number and expression as previously published (Mucke et. al. J Neurosci. 2000 Jun 1; 20(11): 4050-8).
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. The transgene integrated into chromosome 16 causing a 40.7 Kb deletion in an intron of the Zbtb20 (zinc finger and BTB domain containing 20) gene. Founder line 20 has a copy number of greater than 10. 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 five to seven 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 eight to 10 months. Pups born of carrier females have shown an increased mortality rate in our colonies. The Donating Researcher has observed an approximately 15% mortality rate in the first 6 months of life. Video-EEG monitoring of 4 to 7 month old hemizygous transgenic mice, N10+ on the C57BL/6J background, reveals hippocampal hyperexcitability and cortical and hippocampal spontaneous nonconvulsive seizures. The mice are immobile, with no myoclonic behavior observed, during the non-convulsive electroencephalographic seizures. Pentylenetetrazole induced seizures have earlier onset, are more severe and result in more frequent deaths (50% develop fatal status epilepticus) than wildtype controls (Palop et al. Neuron 2007). 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. The resulting transgenic mice were then backcrossed for 12 generations on the C57BL/6J background.
This strain was previously distributed as B6.Cg-Tg(PDGFB-APPSwInd)20Lms/1J. That strain was found to have undergone a loss of transgenic copy number and consequent delayed onset of the phenotype, so this strain was re-imported from the lab of Dr. Lennart Mucke. Transgenic copy number is assayed using a Multiplex TaqMan assay. The transgene integrated into chromosome 16 causing a 40.7 Kb deletion in an intron of the Zbtb20 (zinc finger and BTB domain containing 20) gene. Founder line 20 has a copy number of greater than 10.
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 |
When maintaining a live colony, hemizygous males are bred to wildtype siblings or to C57BL/6J inbred females. Pups born of carrier females have shown an increased mortality rate in our colonies. The Donating Researcher has observed an approximately 15% mortality rate in the first 6 months of life.
When using the J20 mouse strain in a publication, please cite the originating article(s) and include MMRRC stock #34836 in your Materials and Methods section.
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. We do not guarantee breeding performance and therefore suggest that investigators order more than one breeding pair to avoid delays in their research.
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