These TetAPPswe/ind mice express human APP bearing the Swedish and Indiana mutations in a tet-responsive manner. Amyloid pathology is observed when the transgene is expressed. This strain has been shown to be useful in studies correlating temporal expression of mutant APP expression with Alzheimer's-like amyloid pathology.
Dr. David R Borchelt, University of Florida
Genetic Background | Generation |
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Allele Type |
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Transgenic (Inducible, Inserted expressed sequence, Humanized sequence) |
Hemizygotes for this tetO-APPswe/ind transgene are viable and fertile. These transgenic mice express a chimeric mouse/human amyloid precursor protein (APP695) bearing the Swedish (KM570/571NL) and Indiana (V617F) mutations associated with Alzheimer's disease (APP695swe/ind) under the control of a tetracycline-responsive promoter element (TRE; tetO). When hemizygotes are bred with another transgenic mouse expressing either reverse tetracycline-controlled transactivator protein (rtTA) or tetracycline-controlled transactivator protein (tTA) under the regulation of a tissue-specific promoter, APP695swe/ind expression in the target tissue of the bitransgenic offspring can be regulated with the tetracycline analog doxycycline (dox) in the resulting double mutant offspring.
These tetO-APPswe/ind transgenic mice may be useful in studies of Alzheimer's disease and other neurodegenerative diseases.
For example, when bred to a strain expressing tTA in brain tissues (Tg(Camk2a-tTA)1Mmay), bi-transgenic offspring show 10-30 fold greater transgenic APP695swe/ind protein expression than endogenous levels and nearly complete suppression following dox treatment. The donating investigators report some differences in APP695swe/ind expression in bi-transgenic offspring dependent upon which APP695swe/ind founder line was used; line 885 (B6.Cg-Tg(tetO-APPSwInd)885Dbo/Mmjax) shows the highest APP695swe/ind expression with greater dox requirements for transgene suppression, line 102 (B6.Cg-Tg(tetO-APPSwInd)102Dbo/Mmjax) has the greatest sensitivity to dox, and line 107 (B6.Cg-Tg(tetO-APPSwInd)107Dbo/Mmjax) and line 18 are similarly intermediate.
Note that tet alone may affect neuronal degeneration and behavioral phenotypes, depending on the genetic background used (see Han et al, J. Neurosci., 2012).
In an attempt to offer alleles on well-characterized or multiple genetic backgrounds, alleles are frequently moved to a genetic background different from that on which an allele was first characterized. It should be noted that the phenotype could vary from that originally described. We will modify the strain description if necessary as published results become available.
The mouse amyloid beta (A4) precursor protein (App) sequence was first modified to contain a humanized amyloid-beta (Abeta) domain. This mouse/human chimeric APP (called mo/huAPP695 or APP695) was further mutated to incorporate the Swedish (KM570/571NL) and Indiana (V617F) mutations associated with Alzheimer's disease. This APP695swe/ind sequence was placed downstream of the tetracycline-responsive (TRE;tetO) promoter and mouse prion protein exons 1-2. The complete tetracycline-responsive APP695swe/ind transgene (tet-APPswe/ind) was injected into the pronucleus of fertilized eggs from (C57BL/6J x C3HeJ) F1 matings. Transgene positive founders (line 107) were bred to transgenic Camk2a-tTA mice (B6;CBA-Tg(Camk2a-tTA)1Mmay/J) on a B6;CBA mixed genetic background. After 3-4 generations of brother-sister matings, mice harboring only the tet-APPswe/ind transgene were selected and backcrossed to C57BL/6 for at least 10 generations prior to arrival at the MMRRC at The Jackson Laboratory.
Expressed Gene | APP695, amyloid beta (A4) precursor protein (chimeric), mouse/human chimera |
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Site of Expression |
Allele Name | transgene insertion 107, David R Borchelt |
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Allele Type | Transgenic (Inducible, Inserted expressed sequence, Humanized sequence) |
Allele Synonym(s) | tet-APPswe/ind line 107; Tg(tetO-APP*Swe*Ind)107Dbo |
Gene Symbol and Name | Tg(tetO-APPSwInd)107Dbo, transgene insertion 107, David R Borchelt |
Gene Synonym(s) | |
Promoter | tetO, tet operator, |
Expressed Gene | APP695, amyloid beta (A4) precursor protein (chimeric), mouse/human chimera |
Strain of Origin | (C57BL/6J x C3H/HeJ)F1 |
Chromosome | UN |
Molecular Note | The mouse amyloid beta (A4) precursor protein (APP) sequence was modified to contain a humanized amyloid-beta (Abeta) domain. This mouse/human chimeric APP (mo/huAPP695 or APP695) was mutated to incorporate the Swedish (KM570/571NL) and Indiana (V617F) APP mutations associated with Alzheimer's disease. This APP695swe/ind sequence was placed downstream of the tetracycline-responsive (TRE or tetO) promoter and mouse prion protein exons 1-2. Line 107 was established and most thoroughly studied. |
Mutations Made By | Dr. David Borchelt, University of Florida |
When maintained as a live colony, hemizygous mice are bred to C57BL/6J or wildtype siblings.
When using the B6.Cg-Tg(tetO-APPSwInd)107Dbo/Mmjax mouse strain in a publication, please cite the originating article(s) and include MMRRC stock #34846 in your Materials and Methods section.
Facility Barrier Level Descriptions
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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