(B6.Cg-Tg(APPSwFlLon,PSEN1*M146L*L286V)6799Vas/Mmjax x BXD70/RwwJ)F1/J

Stock number: 033259
Product name: AD-BXD 70 , 5xFAD BxD70
Research areas: Mouse/Human Gene Homologs, Neurobiology Research, Research Tools

Description

AD-BXD 70 (Stock No. 033259) mice are the first generation (F1) offspring created by breeding C57BL/6J-congenic females hemizygous for the 5xFAD transgene (Stock No. 008730) to BXD70/TyJ males (Stock No. 007115).

The AD-BXD panel of F1 hybrid mice are an isogenic resource useful for studying the effect of genetic background/diversity on the 5XFAD transgenic model of Alzheimer's disease. This panel allows for the monitoring of phenotypic outcomes in individual mice harboring identical high-risk FAD mutations in human APP and PSEN1 genes, but whose allelic contributions differ across the remainder of the genome.

The AD-BXD panel was originally characterized by the laboratory of Dr. Catherine C. Kaczorowski (The Jackson Laboratory) in Neuner et al. 2019 Neuron 101:1 [PMID:30595332]. Please see that publication for specific characterization of each mouse line.

Detailed description

For the AD-BXD 70 mouse line (Stock No. 033259), The Jackson Laboratory will distribute the first generation (F1) offspring created by breeding C57BL/6J-congenic females hemizygous for the 5xFAD transgene (Stock No. 008730) to BXD70/TyJ males (Stock No. 007115).

The AD-BXD panel is an Alzheimer's disease mouse reference panel of first generation (F1) offspring created by breeding females from the C57BL/6J-congenic 5xFAD strain (Stock No. 008730) to males from 27 different BXD recombinant inbred strains - with the goal being to generate genetically diverse but isogenic F1 offspring.

The AD-BXD panel combines two well-established resources - [i] the 5XFAD transgenic line on the C57BL/6J-congenic background which recapitulates various aspects of human Alzheimer's disease (including amyloid-β42 accumulation, cognitive deficits and neuron loss) and [ii] the BXD genetic reference panel, a large and well-characterized series of recombinant inbred strains derived from an initial crossing between the C57BL/6J (Stock No. 000664) and DBA/2J (Stock No. 000671) inbred strains. The BXD panel segregates for more than 4.8 million sequence variants, including many in genes known to confer risk for AD.

Therefore, the AD-BXD panel of F1 hybrid mice are an isogenic resource useful for studying the effect of genetic background/diversity on the 5XFAD transgenic model of Alzheimer's disease. This panel allows for the monitoring of phenotypic outcomes in individual mice harboring identical high-risk FAD mutations in human APP and PSEN1 genes, but whose allelic contributions differ across the remainder of the genome.

The AD-BXD panel was originally characterized by the laboratory of Dr. Catherine C. Kaczorowski (The Jackson Laboratory) in Neuner et al. 2019 Neuron 101:1 [PMID:30595332]. Please see that publication for specific characterization of each mouse line.

Development

The AD-BXD panel is an Alzheimer's disease mouse reference panel of first generation (F1) offspring created by breeding females from the C57BL/6J-congenic 5xFAD strain (Stock No. 008730) to males from 27 different BXD recombinant inbred strains - with the goal being to generate genetically diverse but isogenic F1 offspring.

For Stock No. 033259 (AD-BXD 70), The Jackson Laboratory will distribute the first generation (F1) offspring created by breeding C57BL/6J-congenic females hemizygous for the 5xFAD transgene (Stock No. 008730) to BXD70/TyJ males (Stock No. 007115).

Allele

Symbol: Tg(APPSwFlLon,PSEN1*M146L*L286V)6799Vas
Name: transgene insertion 6799, Robert Vassar
MGI accession ID: MGI:3693208
Generation method: Transgenic
Attributes: Inserted expressed sequence; Humanized sequence
Synonyms: 5XFAD; 5XFAD APP/PS1; 5XFAD line Tg6799; Tg(APP*Swe*Fl*Lon,PSEN1*M146L*L286V)6799Vas; Tg-5xFAD; Tg6799
Marker symbol: Tg(APPSwFlLon,PSEN1*M146L*L286V)6799Vas
Marker name: transgene insertion 6799, Robert Vassar
Marker synonyms: 5XFAD; 5XFAD line Tg6799; Tg6799
Chromosome: 3
Strain of origin: (C57BL/6 x SJL)F1
Expressed genes: PSEN1,presenilin 1,human; APP695,amyloid beta (A4) precursor protein (chimeric),mouse/human chimera
Site of expression: Expression is directed to the brain by neural-specific elements of the mouse Thy1 promoter

Molecular note: Four familial Alzheimer disease- (FAD-) associated mutations were introduced into a single human amyloid precursor protein cDNA: the "Swedish" double mutation (K670N/M671L); the "Florida" mutation (I716V); and the "London" mutation (V717I). Two FAD-associated mutations, M146L and L286V, likewise were introduced into a human presenilin 1 cDNA. Each cDNA was then cloned independently into the mouse thymus cell antigen 1 gene, replacing a segment that contains thymus-specific elements so that expression of the transgenes is targeted only to the brain. Equal molar amounts of the two transgenes were coinjected into pronuclei of single-celled embryos.
General note: Three transgenic lines coexpressing the APP and PSEN1 proteins at high, medium and low levels, respectively designated Tg6799, Tg7031, and Tg7092, were propagated for analysis, most of which employed Tg6799.

Phenotypic Similarity to Human Syndrome: Macular Degeneration, Age-Related J:214858.