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.