Alport综合征是一种遗传性慢性人类肾脏疾病，以肾小球基底膜异常为特征。这种疾病是由COL4A3、COL4A4或COL4A5基因突变引起的。Col4 α 3、Col4 α 4和Col4 α 5的敲除小鼠是为研究 Alport 综合征而开发和表征的。然而，疾病进展和药物治疗的效果取决于遗传变异性。该模型仅对鼠标可靠。在这项研究中，我们利用 rGONAD 技术创建了一种新的 Alport 综合征大鼠模型，该模型产生了Col4缺失的大鼠α 5基因。Col4 α 5缺陷大鼠出现血尿、蛋白尿、BUN、Cre高水平，然后在18～28周龄时死亡（半合子突变雄性）。组织学和超微结构分析显示异常，包括壁细胞增生、系膜硬化和间质纤维化。然后，我们证明了在Col4α5缺陷大鼠中，IV 型胶原蛋白的 α3/α4/α5 (IV) 和 α5/α5/α6 (IV) 链被破坏。因此，Col4 α 5突变大鼠是 Alport 综合征模型的可靠候选者，可作为肾脏疾病机制的基础，并进一步确定人类肾脏疾病的潜在治疗靶点。

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Alport syndrome is an inherited chronic human kidney disease, characterized by glomerular basement membrane abnormalities. This disease is caused by mutations in COL4A3, COL4A4, or COL4A5 gene. The knockout mice for Col4α3, Col4α4, and Col4α5 are developed and well characterized for the study of Alport syndrome. However, disease progression and effects of pharmacological therapy depend on the genetic variability. This model was reliable only to mouse. In this study, we created a novel Alport syndrome rat model utilizing the rGONAD technology, which generated rat with a deletion of the Col4α5 gene. Col4α5 deficient rats showed hematuria, proteinuria, high levels of BUN, Cre, and then died at 18 to 28 weeks of age (Hemizygous mutant males). Histological and ultrastructural analyses displayed the abnormalities including parietal cell hyperplasia, mesangial sclerosis, and interstitial fibrosis. Then, we demonstrated that α3/α4/α5 (IV) and α5/α5/α6 (IV) chains of type IV collagen disrupted in Col4α5 deficient rats. Thus, Col4α5 mutant rat is a reliable candidate for the Alport syndrome model for underlying the mechanism of kidney diseases and further identifying potential therapeutic targets for human renal diseases.