Appd2^FVB/NCr
QTL Variant Detail

Summary

• QTL variant: Appd2^FVB/NCr
• Name: APP associated premature death 2; FVB/NCr
• MGI ID: MGI:3663099
• QTL: Appd2 Location: Chr14:5945552-30114862 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

Variant origin

• Strain of Specimen: FVB/NCr

Variant description

• Allele Type: QTL
• Mutation: Undefined
• This allele confers premature death in the presence of Tg(APPSWE)2576Kahs compared to 129S6. (J:101523)

Notes

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

J:101523

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.

References

• 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)