Department of Pharmacology, The University of Mississippi Medical Center, United States; Department of Neurology, The University of Mississippi Medical Center, United States.
Med Hypotheses. 2017 Sep;106:6-9. doi: 10.1016/j.mehy.2017.06.020. Epub 2017 Jun 27.
Nephron endowment, the total number of nephrons an individual is born with, is determined by both genetic and environmental factors during embryonic development. In 1988, Brenner hypothesized that there was an inverse relationship between nephron number and hypertension. Over the course of one's lifetime it is predicted that even healthy individuals will lose a significant percentage of nephrons as part of normal aging. Thus, a low nephron endowment at birth or in combination with age- or disease-related nephron loss could pre-dispose individuals to the development of hypertension. Currently, it is not clear what minimal number (ie, threshold) of nephrons is associated with susceptibility to glomeruli injury or hypertension, due in part to the lack of relevant animal models. The BPH2 mouse is a unique genetic model of hypertension that has a normotensive line (BPN3 mice) as well as a hypotensive line (BPL1 mice) derived from the original breeding of eight common inbred strains of mice. Thus, we hypothesize that the differences in blood pressure observed in BPH2, BPN3, and BPL1 mice will correlate inversely with nephron number as predicted by the Brenner hypothesis. If our hypothesis is true, then the BPH2 mouse model will provide a unique experimental model to study the impact of nephron endowment and nephron number on susceptibility to renal injury and hypertension.
肾单位数量，即个体在出生时所拥有的肾单位总数，由胚胎发育过程中的遗传和环境因素共同决定。1988 年，Brenner 提出假说，即肾单位数量与高血压之间存在负相关关系。在人的一生中，即使是健康个体，也会随着正常衰老而失去相当一部分肾单位。因此，出生时肾单位数量较少，或与年龄或疾病相关的肾单位损失相结合，可能使个体易患高血压。目前，由于缺乏相关的动物模型，尚不清楚与肾小球损伤或高血压易感性相关的最小肾单位数量（即阈值）是多少。BPH2 小鼠是一种独特的高血压遗传模型，它有一个正常血压系（BPN3 小鼠）和一个低血压系（BPL1 小鼠），源自最初对八种常见近交系小鼠的杂交选育。因此，我们假设在 BPH2、BPN3 和 BPL1 小鼠中观察到的血压差异将与 Brenner 假说所预测的肾单位数量呈负相关。如果我们的假设是正确的，那么 BPH2 小鼠模型将为研究肾单位数量和肾单位数量对肾脏损伤和高血压易感性的影响提供一个独特的实验模型。
