Mouse Strain Datasheet
Mouse Strain Datasheet
These double transgenic mice express human presenilin 1 and a chimeric amyloid precursor protein. Brain tissue of these mice exhibit amyloid deposits resembling those observed in Alzheimer's disease.
Dr. David R Borchelt, University of Florida
| Genetic Background | Generation |
|---|---|
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| Allele Type |
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| Transgenic (Inserted expressed sequence, Humanized sequence) |
| Allele Type |
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| Transgenic (Inserted expressed sequence, Humanized sequence) |
These transgenic mice express human presenilin 1 (A246E variant) and a chimeric amyloid precursor protein (APPSwe). The mouse prion protein promoter directs expression of both transgenes. Elevated levels of the AB1-42(43) peptide is detected in brain homogenates. By nine months of age, histological examination of brain tissue reveals numerous amyloid deposits resembling those observed in the brains of patients with Alzheimer's disease (AD). The number of amyloid deposits increases dramatically between the ages of 10 and 12 months. These mice provide a useful model for studying the underlying mechanism of amyloid deposition, a process implicated in AD.
Mouse pronuclei (B6C3H) were injected with an expression plasmid containing a mouse prion promoter and a cDNA encoding human presenilin 1 bearing the A246E substitution (line N-5). Another subset of mouse pronuclei (B6C3H) were injected with an expression plasmid containing a cDNA encoding a chimeric amyloid beta (A4) precursor protein, also regulated by the mouse prion promoter (line C3-3). The chimeric APP molecule was created by replacing sequences encoding the Abeta domain of the murine sequence with the cognate sequences of the human gene (mutations K595N, M596L). The two transgenic lines were subsequently mated to generate the double transgenic.
| Expressed Gene | PSEN1, presenilin 1, human |
|---|---|
| Site of Expression | |
| Expressed Gene | APP695, amyloid beta (A4) precursor protein (chimeric), mouse/human chimera |
| Site of Expression |
| Allele Name | transgene insertion 5, David R Borchelt |
|---|---|
| Allele Type | Transgenic (Inserted expressed sequence, Humanized sequence) |
| Allele Synonym(s) | transgene insertion 5, David R Borchelt; Tg(PSEN1)5Dbo |
| Gene Symbol and Name | Tg(PSEN1)5Dbo, transgene insertion 5, David R Borchelt |
| Gene Synonym(s) | PS1A246E; PS1 A246E; PS1-A246E; PS1/A246E; Hu PS1-A246E |
| Promoter | Prnp, prion protein, mouse, laboratory |
| Expressed Gene | PSEN1, presenilin 1, human |
| Strain of Origin | Not Specified |
| Chromosome | UN |
| General Note | This line was generated from founder number N-5.
Transgenic mice that are also transgenic for Tg(APP695)3Dbo express both human presenilin 1 (A246E variant) and a chimeric amyloid precursor protein (APPSwe) under direction of the mouse prion protein promoter. Elevated levels of the AB1-42(43) peptide are detected in brain homogenates. By nine months of age, histological examination of brain tissue from these mice reveals numerous amyloid deposits resembling those observed in the brains of patients with Alzheimer's disease (AD). The number of amyloid deposits increases dramatically between the ages of 10 and 12 months. |
| Molecular Note | The transgene consists of a mouse prion promoter and a cDNA encoding human presenilin 1 bearing the A246E substitution found in familial Alzheimer's disease (FAD). Transgene expression was verified by Northern and Western blot analysis of brain extracts derived from transgenic animals. |
| Mutations Made By | Dr. David Borchelt, University of Florida |
| Allele Name | transgene insertion 3, David R Borchelt |
|---|---|
| Allele Type | Transgenic (Inserted expressed sequence, Humanized sequence) |
| Allele Synonym(s) | transgene insertion 3, David R Borchelt; Tg(APP695)3Dbo |
| Gene Symbol and Name | Tg(APP695)3Dbo, transgene insertion 3, David R Borchelt |
| Gene Synonym(s) | APP695; APPswe; Mo/HuAPPswe; APP695swe; line C3-3 |
| Promoter | Prn, prion protein readthrough transcript, mouse, laboratory |
| Expressed Gene | APP695, amyloid beta (A4) precursor protein (chimeric), mouse/human chimera |
| Strain of Origin | (C57BL/6J x C3H/HeJ)F2 |
| Chromosome | UN |
| General Note | Three transgenic lines were generated and designated by the authors lines Q2-2, E1-2 (Tg(Prnp-App/APPswe)E1-2Dbo) and C3-3.
This line was generated from founder number C3-3. Transgenic mice develop amyloid deposits in brain tissue by 18-20 months of age. Transgenic mice that are also transgenic for Tg(PSEN1)5Dbo express both human presenilin 1 (A246E variant) and a chimeric amyloid precursor protein (APPSwe) under direction of the mouse prion protein promoter. Elevated levels of the AB1-42(43) peptide are detected in brain homogenates. By nine months of age, histological examination of brain tissue from these mice reveals numerous amyloid deposits resembling those observed in the brains of patients with Alzheimer's disease (AD). The number of amyloid deposits increases dramatically between the ages of 10 and 12 months. |
| Molecular Note | The transgene is composed of a cDNA encoding a chimeric APP protein regulated by the mouse prion promoter. The chimeric APP molecule was created by replacing sequences encoding the Abeta domain of a 695 amino acid isoform of the murine sequence with the cognate sequences of the human gene (mutations K595N, M596L). The human mutations are found in familial Alzheimer's disease. Transgene expression was observed in the brain and heart by Western blot analysis using a monoclonal antibody recognizing the human Abeta region. |
| Mutations Made By | Dr. David Borchelt, University of Florida |
The strain originated on a mixed B6;C3H background. The investigator maintains the line by mating double transgenics to C3B6F1 mice. The double transgenics are hemizygous; they are not linked (only 1 in 4 pups is a double transgenic); and the integration site is unknown. Reproduction is excellent. This line is maintained by mating (APP695/0, +/+) x (+/+, PSEN1/0) (or reciprocal) to distribute mice APP695/+, PSEN1/+. Expected coat colors: agouti, black. MMRRC will supply 1) hemizygous APP695, wildtype PSEN1; 2) wildtype APP695, hemizygous PSEN1; and 3) double hemizygotes. Breeder pairs will be the hemizygous APP695, wildtype PSEN1 and the wildtype APP695, hemizygous PSEN1 from the colony (and the reciprocal). Control mice can be generated from this breeding pair. Alternatively, investigators can consider B6C3F1/J.
When using the B6C3-Tg(APP695)3Dbo Tg(PSEN1)5Dbo/Mmjax mouse strain in a publication, please cite the originating article(s) and include MMRRC stock #41848 in your Materials and Methods section.
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