Amyloidosis modifier genes in the less amyloidogenic a/j mouse strain.
Apolipoprotein A-II is deposited as an amyloid fibril in aged mice (senile AApoAII amyloidosis). Although mouse strains with the apolipoprotein A-II c allele (Apoa2(c)) generally develop early-onset and severe senile amyloidosis, the A/J strain shows significantly less amyloid deposition. To identify genes that modify spontaneous amyloidosis development in the A/J mouse, we performed a genome-wide screening using hybrid mice derived from A/J and SAMP1 mice, which have Apoa2(c) and age-associated severe amyloid deposition. Our genetic analysis revealed that the lower levels of amyloidosis in the A/J strain were polygenically controlled. We found two chromosome locations associated with amyloidosis. One of these regions was in the chromosome 19 telomeric region, where the A/J alleles modify amyloidosis in an additive manner. The second region was in the chromosome 4 telomeric region, where the A/J alleles modify amyloidosis in a dominant manner. Perlecan and group II secretory phospholipase A2, located on the significantly linked region of chromosome 4, were compared in this study. These findings are for understanding the genetic mechanism of amyloidosis-related diseases and their prevention.
Guo
Zhanjun
Z
Department of Aging Biology, Shinshu University Graduate School of Medicine, Matsumoto, Japan.
Mori
Masayuki
M
Fu
Xiaoying
X
Yao
Junjie
J
Xing
Yanming
Y
Korenaga
Tatsumi
T
Li
Guixin
G
Matsushita
Takatoshi
T
Hosokawa
Masanori
M
Higuchi
Keiichi
K
D000682:Amyloid / Q000378:metabolism; D000686:Amyloidosis / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D000818:Animals; D016633:Apolipoprotein A-II / Q000235:genetics* / Q000378:metabolism; D002678:Chimera / Q000235:genetics; D002874:Chromosome Mapping; D005260:Female; D005809:Genes, Regulator; D020022:Genetic Predisposition to Disease; D005820:Genetic Testing; D019812:Heparan Sulfate Proteoglycans / Q000378:metabolism; D007178:Inbreeding; D008099:Liver / Q000378:metabolism / Q000473:pathology; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D010741:Phospholipases A / Q000378:metabolism; D054467:Phospholipases A2; D013045:Species Specificity
D000682:Amyloid; D016633:Apolipoprotein A-II; D019812:Heparan Sulfate Proteoglycans; C071927:perlecan; D010741:Phospholipases A; D054467:Phospholipases A2