THE TRANSGENIC SAD MOUSE - A MODEL OF HUMAN SICKLE-CELL GLOMERULOPATHY
THE TRANSGENIC SAD MOUSE - A MODEL OF HUMAN SICKLE-CELL GLOMERULOPATHY
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DOI：
10.1038/ki.1994.403
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发表时间：
1994-11-01
影响因子：
19.6
通讯作者：
TRUDEL, M
中科院分区：
文献类型：
--
作者：
DEPAEPE, ME;TRUDEL, M
表达修饰的镰状血红蛋白 Hb SAD 的转基因 SAD 小鼠表现出体内血红蛋白聚合和红细胞镰状化。在本研究中，对 SAD 小鼠进行了功能和形态学肾脏分析，以便将 SAD 小鼠的肾脏病理学与人类疾病进行比较。 SAD小鼠表现出肾含铁血黄素沉着症、微血管闭塞、血管血栓形成、皮质梗塞和乳头坏死。在髓质中，可以观察到血红蛋白聚合物与罕见的红细胞镰状化，这可以解释不存在显着的肾脏浓缩缺陷，而在人类中，血管化网络的差异导致更广泛的镰状化。大多数动物会出现肾小球肥大和系膜硬化，其频率和严重程度随着年龄的增长而增加。肾小球损伤与功能缺陷相关，包括血液尿素氮水平升高和非选择性蛋白尿。 SAD 小鼠的肾小球病变与镰状细胞性肾小球硬化症极为相似，镰状细胞性肾小球硬化症是人类镰状细胞病最严重的肾脏并发症。总之，SAD小鼠是人类镰状细胞性肾小球病的血栓形成和肾小球硬化并发症的有价值的模型，可用于病理生理学研究，并最终用于预防和治疗研究。
The transgenic SAD mouse which expresses a modified sickle hemoglobin, Hb SAD, displays in vivo hemoglobin polymerization and erythrocyte sickling. In the present study functional and morphological renal analyses were performed in SAD mice in order to compare the renal pathology of SAD mice with the human disease. The SAD mice display renal hemosiderosis, microvascular occlusions, vascular thrombosis, cortical infarcts and papillary necrosis. In the medulla, hemoglobin polymers could be observed with infrequent erythrocyte sickling, which may explain the absence of significant renal concentration defect, whereas in humans, the difference in the vascularization network leads to more extensive sickling. Most animals develop glomerular hypertrophy and mesangial sclerosis which increases in frequency and severity with age. The glomerular damage is associated with functional defects, including increased blood urea nitrogen levels and non-selective proteinuria. The glomerular lesions of SAD mice strikingly mimick sickle cell glomerulosclerosis, the most severe renal complication of sickle cell disease in humans. In summary, the SAD mouse is a valuable model of the thrombotic and glomerulosclerotic complications of human sickle cell glomerulopathy and can serve for pathophysiologic studies, and, eventually, for prevention and therapy investigation.