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QTL Variant Detail
QTL variant: Appd2FVB/NCr
Name: APP associated premature death 2; FVB/NCr
MGI ID: MGI:3663099
QTL: Appd2  Location: Chr14:16523711-30392905 bp  Genetic Position: Chr14, cM position of peak correlated region/allele: 7.08 cM
QTL Note: genome coordinates based on the boundaries of the QTL region
Strain of Specimen:  FVB/NCr
Allele Type:    QTL
Mutation:    Undefined
    This allele confers premature death in the presence of Tg(APPSWE)2576Kahs compared to 129S6. (J:101523)
View phenotypes for all genotypes (concatenated display).

Mapping and Phenotype information for this QTL, its variants and associated markers


Linkage analysis was performed on 44 short surviving and 44 long surviving animals from a FVB/NCr x (FVB/NCr x 129S6-Tg(APPSWE)2576Kahs)F1 backcross to identify QTL modifying the effect of the Alzheimer's disease transgene Tg(APPSWE)2576Kahs. Parental strain 129S6- Tg(APPSWE)2576Kahs exhibits a milder disease course, namely longer survival time and decreased age-related spatial and memory deficits. In contrast, Tg(APPSWE)2576Kahs on an FVB/NCr genetic background results in premature death by 100 days of age. Backcross animals were genotyped for 76 microsatellite markers at a resolution of 22.4 cM. Linkage was detected on chromosomes 9, 10, and 14. An additional 79 animals from a (FVB/NCr x 129S6- Tg(APPSWE)2576Kahs)F2 intercross were analyzed to confirm and refine the QTLs.

Significant linkage to age at death mapped to 21 cM on mouse Chromosome 9 near D9Mit285 (LRS=14). This locus is named Appd1 (APP associated premature death 1). FVB/NCr-derived alleles confer premature death. Previously identified QTLs Pid2 (17 cM) and Azdm3 (33.9 cM) map near Appd1.

A locus exhibiting significant linkage to age at death was detected at 11 cM on mouse Chromosome 14 between D14Mit98 and D14Mit127 (LRS=18.3). This locus is named Appd2 (APP associated premature death 2). FVB/NCr-derived alleles confer premature death. Plau is a potential candidate gene for Appd2. The Appd2 interval is syntenic to a region of human Chromosome 10 associated with late-onset Alzheimer's disease and plasma amyloid-beta levels in humans.

Original:  J:101523 Krezowski J, et al., Identification of loci determining susceptibility to the lethal effects of amyloid precursor protein transgene overexpression. Hum Mol Genet. 2004 Sep 15;13(18):1989-97
All:  1 reference(s)

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