LINKAGE OF PROTECTION AGAINST AMYLOID FIBRIL FORMATION IN THE MOUSE TO A SINGLE, AUTOSOMAL-DOMINANT GENE

被引：17

作者：

GONNERMAN, WA

ELLIOTTBRYANT, R

CARRERAS, I

SIPE, JD

CATHCART, ES

机构：

[1] EN ROGERS MEM VET AFFAIRS HOSP,BEDFORD,MA 01730

[2] BOSTON UNIV,SCH MED,DEPT BIOCHEM,BOSTON,MA 02118

[3] BOSTON UNIV,SCH MED,DEPT MED,BOSTON,MA 02118

来源：

JOURNAL OF EXPERIMENTAL MEDICINE | 1995年 / 181卷 / 06期

关键词：

D O I：

10.1084/jem.181.6.2249

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

100102 ;

摘要：

Inbred strains of mice provide a model for studies of the pathogenesis of amyloid A (AA) amyloidosis. All susceptible strains of mice described to date codominantly express two serum amyloid A (apoSAA) isoforms, apoSAA(1) and apoSAA(2), of which only apoSAA(2) serves as a precursor for amyloid fibrils. In previous studies, we have shown that the CE/J strain, which produces a single, novel apoSAA isoform, apoSAA(CE/J), is amyloid resistant. In the present study amyloid-resistant CE/J females were mated with amyloid-susceptible CBA/J males to produce F1 hybrid offspring which were then backcrossed to the parental CBA/J mouse strain. Amyloid susceptibility was determined in 30 backcrossed mice 72 h after injection of murine amyloid enhancing factor and silver nitrate. ApoSAA isoforms in plasma were separated by isoelectric focusing gel electrophoresis and visualized after immunoblotting with anti-AA antiserum. Amyloid A fibrils in spleen homogenates were denatured by formic acid and AA protein was quantified by ELISA using anti-mouse apoSAA antibodies. Values <5 apoSAA equivalent units were considered negative. 13 mice expressed an apoSAA(1) and apoSAA(2) doublet characteristic of CBA/J mice, whereas 17 mice, expressed the apoSAA(CE/J) isoform codominantly with apoSAA(1) and apoSAA(2). The correlation of amyloid resistance to expression of the apoSAA(CE/J) isoform was absolute (17/17 were negative; mean score 2.6 +/- 0.17 [standard error of the mean] apoSAA equivalent units) and the correlation between amyloid susceptibility and the expression of apoSAA(2)/apoSAA(1) was also striking (12/13 were amyloid positive; mean score 47.9 +/- 9.0 [standard error of the mean] apoSAA equivalent units (P <0.001). This is not significantly different from the 50% segregation of apoSAA phenotypes expected for linkage to a single gene. These results indicate that a single gene governs apoSAA(CE/J) expression and thus confers protection against amyloid deposition even in the presence of apoSAA(1) and apoSAA(2) isoforms and show for the first time that resistance to AA amyloidosis is a dominant trait governed by a single gene.

引用

页码：2249 / 2252

页数：4

共 30 条

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