Transmission of amyloidosis in offspring of mice with AApoAII amyloidosis
Transmission of amyloidosis in offspring of mice with AApoAII amyloidosis
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DOI：
10.2353/ajpath.2006.050350
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发表时间：
2006-03-01
影响因子：
6
通讯作者：
Fu, XY
中科院分区：
文献类型：
--
作者：
Korenaga, T;Yan, JM;Fu, XY
预先存在的淀粉样纤维可以诱导内源性前体蛋白在体内的进一步聚合。因此，淀粉样纤维（AApoAII）的传输可能会诱导内源性载脂蛋白A-II的构象变化，并加速小鼠老年性淀粉样变性中的淀粉样蛋白沉积。为了表征遗传性，我们检测了注射AApoAII的母鼠后代的淀粉样变性，这些母鼠具有载脂蛋白A-II基因的淀粉样蛋白Apoa 2（c）等位基因。在4个月大时，在注射淀粉样蛋白原纤维的母亲所生和喂养的后代的肠道中检测到淀粉样蛋白沉积，此后沉积强度增加。在未注射对照组母体的后代中未检测到淀粉样蛋白沉积。在未注射淀粉样蛋白原纤维但由注射淀粉样蛋白原纤维的母亲喂养的母亲所生的后代中也观察到加速的淀粉样变性。然而，这在注射淀粉样蛋白纤维的母亲所生的后代中没有观察到，而是由对照母亲喂养。这种寄养排除了通过胎盘的垂直传播，表明在哺乳期存在加速淀粉样变性的因素。此外，从注射淀粉样蛋白原纤维的母鼠获得的乳汁在幼鼠中诱导AApoAII淀粉样变性，并且透射电子显微镜在注射淀粉样蛋白原纤维的母鼠的乳汁中检测到面条样淀粉样蛋白原纤维。这些结果提供了重要的洞察淀粉样疾病的病因和发病机制。
Pre-existing amyloid fibrils can induce further polymerization of endogenous precursor proteins in vivo. Thus, transmission of amyloid fibrils (AApoAII) may induce a conformational change in endogenous apolipoprotein A-II and accelerate amyloid deposition in mouse senile amyloidosis. To characterize transmissibility, we examined amyloidosis in the offspring of AApoAII-injected mother mice that possessed the amyloidogenic Apoa2(c) allele of the apolipoprotein A-II gene. At 4 months of age, amyloid deposits were detected in the intestines of offspring born from and nursed by amyloid fibril-injected mothers, with intensity of deposition increasing thereafter. No amyloid deposits were detected in the offspring of non-injected control mothers. Accelerated amyloidosis was also observed in offspring born from mothers without injection but nursed by amyloid fibril-injected mothers. However, this was not observed in offspring born from amyloid fibril-injected mothers but nursed by control mothers. This fostering excluded vertical transmission through the placenta, suggesting the presence of factors that accelerate amyloidosis during the nursing period. in addition, milk obtained from amyloid fibril-injected mothers induced AApoAII amyloidosis in young mice, and transmission electron microscopy detected noodle-like amyloid fibrils in milk of amyloid fibril-injected mothers. These results provide important insight into the etiology and pathogenesis of amyloid diseases.