Department of Environmental Health Sciences, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, Maryland 21205, USA.
J Appl Physiol (1985). 2012 Feb;112(3):490-500. doi: 10.1152/japplphysiol.01477.2010. Epub 2011 Nov 10.
We have previously shown that the adult DBA/2J and A/J strains of mice differ in carotid body volume and morphology. The question has arisen whether these differences develop during the prenatal or postnatal period. Investigating morphological development of the carotid body and contributing genes in these mice can provide further understanding of the appropriate formation of the carotid body. We examined the carotid body of these mice from 1 day to 4 wk old for differences in volume, morphology, and gene expression of Gdnf family, Dlx2, Msx2, and Phox2b. The two strains showed divergent morphology starting at 1 wk old. The volume of the carotid body increased from 1 wk up to 2 wk old to the level of 4 wk old in the DBA/2J mice but not in the A/J mice. This corresponds with immunoreactivity of LC3, an autophagy marker, in A/J tissues at 10 days and 2 wk. The differences in gene expression were examined at 1 wk, 10 days, and 2 wk old, because divergent growth occurred during this period. The DBA/2J's carotid body at 1 wk old showed a greater expression of Msx2 than the A/J's carotid body. No other candidate genes showed consistent differences between the ages and strains. The difference was not seen in sympathetic cervical ganglia of 1 wk old, suggesting that the difference is carotid body specific. The current study indicates the critical postnatal period for developing distinctive morphology of the carotid body in these mice. Further studies are required to further elucidate a role of Msx2 and other uninvestigated genes.
我们之前已经表明，成年 DBA/2J 和 A/J 品系的小鼠在颈动脉体的体积和形态上存在差异。问题是这些差异是在产前还是产后发展的。研究这些小鼠颈动脉体的形态发育和相关基因可以进一步了解颈动脉体的适当形成。我们检查了这些小鼠从 1 天到 4 周龄的颈动脉体的体积、形态和 Gdnf 家族、Dlx2、Msx2 和 Phox2b 的基因表达差异。这两个品系从 1 周龄开始表现出不同的形态。DBA/2J 小鼠的颈动脉体体积从 1 周到 2 周龄增加到 4 周龄，但 A/J 小鼠没有增加。这与 A/J 组织中自噬标志物 LC3 在 10 天和 2 周时的免疫反应性相对应。在 1 周、10 天和 2 周龄时检查了基因表达的差异，因为在此期间发生了不同的生长。1 周龄的 DBA/2J 颈动脉体的 Msx2 表达高于 A/J 颈动脉体。没有其他候选基因在年龄和品系之间表现出一致的差异。在 1 周龄的交感颈神经节中没有观察到这种差异，这表明这种差异是颈动脉体特异性的。本研究表明，在这些小鼠中，颈动脉体形成独特形态的关键是产后时期。需要进一步研究以进一步阐明 Msx2 和其他未被研究的基因的作用。
