Monoclonal glomerulopathy with features of cryoglobulinemic glomerulopathy in murine multiple myeloma model.

Monoclonal glomerulopathy with features of cryoglobulinemic glomerulopathy in murine multiple myeloma model.
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小鼠多发性骨髓瘤模型中具有冷球蛋白血症性肾小球病特征的单克隆肾小球病。

DOI:
10.1080/01913123.2020.1841349
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发表时间:
2020-11-20
影响因子:
1
通讯作者:
Liu B
Liu B
中科院分区:
工程技术4区
文献类型:
--
作者:
Zhang PL;Herrera GA;Liu B

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与单克隆性轻链相关的肾脏疾病的体内和动物模型有限。VK*MYC转基因模型在50-70周龄的多发性骨髓瘤小鼠中的肾脏受累已有报道,但详细的肾脏病理变化尚未得到很好的报道。本研究采用光镜、免疫荧光染色和电子显微镜技术,对VK*MYC转基因模型大鼠肾脏的病理变化进行了全面研究。与野生型小鼠的肾脏相比,转基因小鼠的肾脏表现为系膜节段性扩张,部分伴有细胞增多,和/或肾小球毛细血管血栓形成。肾小球的Lambda染色强于Kappa轻链染色。在超微结构检查中,转基因小鼠的12个肾脏中有6个显示出丰富的电子致密沉积物。3例位于肾小球毛细血管腔内。大的管腔和内皮下沉积的特征是随机分布的直径长达16 nm的微管结构,总体特征与冷冻球蛋白最一致。综上所述,患有骨髓瘤的VK*MYC小鼠约50%的肾脏具有与单克隆性冷球蛋白血症肾小球疾病最一致的特征。
In vivo and animal models of monoclonal light chain-associated renal diseases are limited. The Vk*MYC transgenic model with multiple myeloma in 50–70 weeks old mice with renal involvement has been reported before, but detailed renal pathologic changes have not been well documented. This study fully investigated pathologic changes in the kidneys of Vk*MYC transgenic model using light microscopy, immunofluorescence stains for kappa and lambda light chains, and electron microscopy. Compared to the kidneys of wild type mice, the kidneys of transgenic mice showed either mesangial segmental expansion, some with associated hypercellularity, and /or thrombotic obstruction of glomerular capillaries. The glomeruli revealed stronger lambda staining than kappa light chain staining. Six out of 12 kidneys from transgenic mice showed abundant electron dense deposits when examined ultrastructurally. The deposits were located in glomerular capillary lumina in 3 cases. Large luminal and subendothelial deposits were characterized by randomly disposed microtubular structures measuring up to 16 nm in diameter, with overall features most consistent with cryoglobulins. In summary, about 50% of kidneys from the Vk*MYC mice with myeloma had features most consistent with monoclonal cryoglobulinemic glomerulopathy.
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