Lipták Nándor, Hoffmann Orsolya Ivett, Skoda Gabriella, Gócza Elen, Kerekes Andrea, Bősze Zsuzsanna, Hiripi László
Animal Biotechnology Department, NARIC Agricultural Biotechnology Institute , Szent-Györgyi A. u. 4, H-2100 Gödöllő , Hungary.
Acta Vet Hung. 2018 Jun;66(2):281-293. doi: 10.1556/004.2018.026.
Focal segmental glomerulosclerosis (FSGS) is a potential cause of nephrotic syndrome both in humans and pet mammals. Glomerulopathy was reported earlier in green fluorescent protein (GFP) transgenic (TG) mice, but glomerulosclerosis has not been examined in GFP TG rabbits so far. In the present study, the potential manifestation of FSGS was investigated in both Venus TG rabbits generated by Sleeping Beauty (SB) transposition and age-matched control New Zealand White (NZW) rabbits. Venus protein fluorescence was detected by confocal microscopy and quantified by microplate reader. Urinalysis, haematology, serum biochemistry and renal histology were performed to assess the signs of FSGS. Higher levels of Venus fluorescence were determined in renal cortex samples than in the myocardium by both methods. Urinalysis revealed proteinuria in Venus heterozygote TG bucks, while Venus homozygote TG bucks developed microscopic haematuria. Supporting the urinalysis data, the histological findings of FSGS (glomerulomegaly and sclerotic glomeruli) were observed in renal cortex sections of Venus TG rabbits. Taken together, Venus TG bucks were diagnosed with FSGS; thus, this type of glomerulopathy could be a common disease in TG animals overexpressing GFP.
局灶节段性肾小球硬化（FSGS）是人类和宠物哺乳动物肾病综合征的一个潜在病因。此前在绿色荧光蛋白（GFP）转基因（TG）小鼠中报道过肾小球病，但迄今为止尚未在GFP TG兔中研究过肾小球硬化。在本研究中，对通过睡美人（SB）转座产生的金星TG兔和年龄匹配的对照新西兰白兔（NZW）进行了FSGS潜在表现的研究。通过共聚焦显微镜检测金星蛋白荧光，并通过酶标仪进行定量。进行尿液分析、血液学、血清生物化学和肾脏组织学检查以评估FSGS的体征。两种方法均测定出肾皮质样本中的金星荧光水平高于心肌中的水平。尿液分析显示金星杂合子TG雄兔存在蛋白尿，而金星纯合子TG雄兔出现镜下血尿。支持尿液分析数据的是，在金星TG兔的肾皮质切片中观察到FSGS的组织学表现（肾小球肿大和硬化性肾小球）。综上所述，金星TG雄兔被诊断为FSGS；因此，这种类型的肾小球病可能是过度表达GFP的TG动物中的常见疾病。
