Pathology of Berkeley sickle cell mice: similarities and differences with human sickle cell disease
Pathology of Berkeley sickle cell mice: similarities and differences with human sickle cell disease
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DOI：
10.1182/blood-2005-07-2839
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发表时间：
2006-02-15
期刊：
影响因子：
20.3
通讯作者：
Coller, BS
中科院分区：
文献类型：
--
作者：
Manci, EA;Hillery, CA;Coller, BS
由于伯克利镰状细胞小鼠被用作人类镰状细胞疾病的动物模型，我们调查了这些动物在6个月内的组织病理学进展，并将这些发现与在患有镰状细胞疾病的人类上发表的结果进行了比较。小鼠研究组由野生型混合C57BI/6-SV129(对照组)小鼠和镰状细胞(SS)小鼠(α(-/-)、β(-/-)、转基因+)组成，雌雄不一，1~6月龄。SS小鼠在红细胞性镰刀样改变、血管扩张、血管内溶血、充血、心脏肿大、肾小球硬化、内脏充血、出血、多器官梗塞、神经元固缩和进行性铁质沉着等方面与人类镰状细胞病相似。脑血流灌注研究显示SS小鼠血脑屏障通透性增加。SS小鼠与人镰状细胞病的不同之处在于脾肿大，脾造血，肝梗死较严重，肺部表现较轻，无明显血管内膜增生，仅有血管中层肥大的趋势。由一种与引起镰刀状血红蛋白无关的纯合子突变(Rd1)引起的早期视网膜变性在一些Berkeley小鼠中是偶然发现的。虽然我们的研究加强了这一模型的基本力量，但在将其与人类镰状细胞疾病相提并论时，值得仔细考虑的显著差异。
Because Berkeley sickle cell mice are used as an animal model for human sickle cell disease, we investigated the progression of the histopathology in these animals over 6 months and compared these findings to those published in humans with sickle cell disease. The murine study groups were composed of wild-type mixed C57BI/6-SV129 (control) mice and sickle cell (SS) mice (alpha(-/-), beta(-/-), transgene +) of both sexes and between 1 and 6 months of age. SS mice were similar to humans with sickle cell disease in having erythrocytic sickling, vascular ectasia, intravascular hemolysis, exuberant hematopolesis, cardiomegaly, glomerulosclerosis, visceral congestion, hemorrhages, multiorgan infarcts, pyknotic neurons, and progressive siderosis. Cerebral perfusion studies demonstrated increased blood-brain barrier permeability in SS mice. SS mice differed from humans with sickle cell disease in having splenomegaly, splenic hematopoiesis, more severe hepatic infarcts, less severe pulmonary manifestations, no significant vascular intimal hyperplasia, and only a trend toward vascular medial hypertrophy. Early retinal degeneration caused by a homozygous mutation (rd1) independent from that causing sickle hemoglobin was an incidental finding in some Berkeley mice. While our study reinforces the fundamental strength of this model, the notable differences warrant careful consideration when drawing parallels to human sickle cell disease.