B6C3-Tg(APP695)3Dbo Tg(PSEN1)5Dbo/Mmjax

Stock number: 003378
Research areas: Mouse/Human Gene Homologs, Neurobiology Research

Description

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.

Detailed description

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.

Development

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.

Allele

Symbol: Tg(APP695)3Dbo
Name: transgene insertion 3, David R Borchelt
MGI accession ID: MGI:2447334
Generation method: Transgenic
Attributes: Inserted expressed sequence; Humanized sequence
Marker symbol: Tg(APP695)3Dbo
Marker name: transgene insertion 3, David R Borchelt
Chromosome: UN
Strain of origin: (C57BL/6J x C3H/HeJ)F2
Expressed genes: APP695,amyloid beta (A4) precursor protein (chimeric),mouse/human chimera
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.
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.

Allele

Symbol: Tg(PSEN1)5Dbo
Name: transgene insertion 5, David R Borchelt
MGI accession ID: MGI:2447335
Generation method: Transgenic
Attributes: Inserted expressed sequence; Humanized sequence
Marker symbol: Tg(PSEN1)5Dbo
Marker name: transgene insertion 5, David R Borchelt
Chromosome: UN
Strain of origin: Not Specified
Expressed genes: PSEN1,presenilin 1,human
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.
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.