小鼠老年性淀粉样变性的遗传分析。

Genetic analysis of murine senile amyloidosis.

作者信息

Naiki H, Higuchi K, Shimada A, Takeda T, Nakakuki K

机构信息

Department of Pathology, Fukui Medical School, Japan.

出版信息

Lab Invest. 1993 Mar;68(3):332-7.

PMID:8095565

Abstract

BACKGROUND

Recent studies have suggested that not only the genotypes of apolipoprotein A-II, the precursor protein of murine senile amyloid fibrils, but also other genetic factors may contribute to the pathogenesis of murine senile amyloidosis.

EXPERIMENTAL DESIGN

We investigated the mode of inheritance of murine senile amyloidosis, using 12-month-old and 14-month-old F1, F2 hybrids and backcrosses between SAM-P/1 and SAM-R/1. In SAM-P/1, the senescence process is accelerated and senile amyloidosis is evident, whereas in SAM-R/1, there is a normal aging process and no evidence of senile amyloidosis. In SAM-P/1 and SAM-R/1, the genotypes of apolipoprotein A-II are Gln/Gln and Pro/Pro, respectively, identified by restriction fragment length polymorphism of the apolipoprotein A-II gene for the restriction enzyme Cfr13I.

RESULTS

Among hybrids and backcrosses, no senile amyloidosis was observed histopathologically, in Pro/Pro-type strains. Mild senile amyloidosis sparing the liver and spleen was observed in a significant percentage of Pro/Gln-type strains. Practical senile amyloidosis involving the liver and spleen was observed in all of the Gln/Gln-type strains. Quantitative fluorometric analysis with thioflavine T (Naiki H, Higuchi K, Matsushima K, Shimada A, Chen W-H, Hosokawa M, et al. Lab Invest 1990;62:768-73) revealed that the degree of murine senile amyloid fibril deposition was significantly decreased in the Gln/Gln-type hybrid and backcross strains, as compared with findings in SAM-P/1 and the degree of manifestation of accelerated senescence was significantly lower in the Gln/Gln-type hybrid and backcross strains than in the SAM-P/1.

CONCLUSIONS

Murine senile amyloidosis is linked to the molecular type of apolipoprotein A-II (i.e., Gln-type apolipoprotein A-II), and is transmitted as an autosomal dominant manner with incomplete penetrance. The severity of murine senile amyloidosis is far more advanced in Gln/Gln-type strains than in Pro/Gln-type strains. Other genetic factors that determine the manifestation of accelerated senescence, may significantly contribute to the degree of murine senile amyloidosis.

摘要

背景

最近的研究表明，不仅小鼠衰老淀粉样原纤维的前体蛋白载脂蛋白A-II的基因型，其他遗传因素也可能在小鼠衰老淀粉样变性的发病机制中起作用。

实验设计

我们使用12个月和14个月大的F1、F2杂种以及SAM-P/1和SAM-R/1之间的回交后代，研究了小鼠衰老淀粉样变性的遗传模式。在SAM-P/1中，衰老过程加速且明显出现衰老淀粉样变性，而在SAM-R/1中，衰老过程正常且无衰老淀粉样变性的迹象。在SAM-P/1和SAM-R/1中，通过载脂蛋白A-II基因针对限制性内切酶Cfr13I的限制性片段长度多态性鉴定，载脂蛋白A-II的基因型分别为Gln/Gln和Pro/Pro。

结果

在杂种和回交后代中，在Pro/Pro型菌株中未观察到组织病理学上的衰老淀粉样变性。在相当比例的Pro/Gln型菌株中观察到轻度的、不累及肝脏和脾脏的衰老淀粉样变性。在所有Gln/Gln型菌株中均观察到累及肝脏和脾脏的典型衰老淀粉样变性。用硫黄素T进行的定量荧光分析（Naiki H，Higuchi K，Matsushima K，Shimada A，Chen W-H，Hosokawa M等。实验室研究1990；62：768 - 73）显示，与SAM-P/1中的结果相比，Gln/Gln型杂种和回交菌株中小鼠衰老淀粉样原纤维沉积程度显著降低，并且Gln/Gln型杂种和回交菌株中加速衰老的表现程度明显低于SAM-P/1。