Division of Nephrology, Department of Medicine, Duke University Medical Center, Durham, North Carolina, United States of America.
PLoS One. 2012;7(4):e33942. doi: 10.1371/journal.pone.0033942. Epub 2012 Apr 4.
Akita mice are a genetic model of type 1 diabetes. In the present studies, we investigated the phenotype of Akita mice on the FVB/NJ background and examined urinary nephrin excretion as a marker of kidney injury. Male Akita mice were compared with non-diabetic controls for functional and structural characteristics of renal and cardiac disease. Podocyte number and apoptosis as well as urinary nephrin excretion were determined in both groups. Male FVB/NJ Akita mice developed sustained hyperglycemia and albuminuria by 4 and 8 weeks of age, respectively. These abnormalities were accompanied by a significant increase in systolic blood pressure in 10-week old Akita mice, which was associated with functional, structural and molecular characteristics of cardiac hypertrophy. By 20 weeks of age, Akita mice developed a 10-fold increase in albuminuria, renal and glomerular hypertrophy and a decrease in the number of podocytes. Mild-to-moderate glomerular mesangial expansion was observed in Akita mice at 30 weeks of age. In 4-week old Akita mice, the onset of hyperglycemia was accompanied by increased podocyte apoptosis and enhanced excretion of nephrin in urine before the development of albuminuria. Urinary nephrin excretion was also significantly increased in albuminuric Akita mice at 16 and 20 weeks of age and correlated with the albumin excretion rate. These data suggest that: 1. FVB/NJ Akita mice have phenotypic characteristics that may be useful for studying the mechanisms of kidney and cardiac injury in diabetes, and 2. Enhanced urinary nephrin excretion is associated with kidney injury in FVB/NJ Akita mice and is detectable early in the disease process.
阿特犬鼠是 1 型糖尿病的一种遗传模型。在本研究中，我们研究了 FVB/NJ 背景下阿特犬鼠的表型，并检查了尿足细胞蛋白（nephrin）排泄作为肾脏损伤的标志物。我们将雄性阿特犬鼠与非糖尿病对照进行了比较，以研究其肾脏和心脏疾病的功能和结构特征。我们在两组中都测定了足细胞数量和凋亡以及尿足细胞蛋白排泄。雄性 FVB/NJ 阿特犬鼠在 4 周和 8 周龄时分别出现持续高血糖和白蛋白尿。这些异常伴随着 10 周龄阿特犬鼠的收缩压显著升高，这与心脏肥大的功能、结构和分子特征有关。到 20 周龄时，阿特犬鼠的白蛋白尿、肾脏和肾小球肥大增加，足细胞数量减少。在 30 周龄的阿特犬鼠中观察到轻度至中度肾小球系膜扩张。在 4 周龄的阿特犬鼠中，高血糖的发生伴随着足细胞凋亡增加和尿中足细胞蛋白排泄增加，而在白蛋白尿发生之前。在 16 周和 20 周龄的白蛋白尿阿特犬鼠中，尿足细胞蛋白排泄也显著增加，与白蛋白排泄率相关。这些数据表明：1. FVB/NJ 阿特犬鼠具有表型特征，可能有助于研究糖尿病中肾脏和心脏损伤的机制；2. 增强的尿足细胞蛋白排泄与 FVB/NJ 阿特犬鼠的肾脏损伤有关，并且在疾病过程的早期即可检测到。
