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bioRxiv · 10.1101/2021.04.13.439726

Creation of X-linked Alport Syndrome Rat Model with Col4a5 Deficiency

Namba, M.·Kobayashi, T.·Kohno, M.·Koyano, T.·Hirose, T.·Fukushima, M.·Matsuyama, M.
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Abstract

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 Col43, Col44, and Col45 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 is reliable only to mice. Therefore in this study, we created a novel Alport syndrome rat model utilizing rGONAD technology. Col45 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 3/4/5 (IV) and 5/5/6 (IV) chains of type IV collagen disrupted in the Col45 deficient rats. Moreover, immunofluorescence analyses revealed that some glomeruli of Col45 mutant rats were found to be disrupted from postnatal day 0. Thus, Col45 mutant rat is a reliable candidate for Alport syndrome model for underlying the mechanism of renal diseases and further identifying potential therapeutic targets for human renal diseases.

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Namba, M., Kobayashi, T., Kohno, M., Koyano, T., Hirose, T., Fukushima, M., Matsuyama, M.. 2021-04-14. Creation of X-linked Alport Syndrome Rat Model with Col4a5 Deficiency. https://doi.org/10.1101/2021.04.13.439726

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