Pediatric obstructive sleep apnea (OSA), a relatively common sleep-related breathing disorder (SRBD) affecting approximately 1-5% of children, is often caused by anatomical obstruction and/or collapse of the nasal and/or pharyngeal airways. The resulting sleep disruption and intermittent hypoxia lead to various systemic morbidities. Predicting the development of OSA from craniofacial features alone is currently not possible and a controversy remains if upper airway obstruction facilitates reduced midfacial growth or vice-versa. Currently, there is no rodent model that recapitulates both the development of craniofacial abnormalities and upper airway obstruction to address these questions. Here, we describe that mice with a neural crest-specific deletion of Bmp7 (Bmp7^ncko) present with shorter, more acute angled cranial base, midfacial hypoplasia, nasal septum deviation, turbinate swelling and branching defects, and nasal airway obstruction. Interestingly, several of these craniofacial features develop after birth during periods of rapid midfacial growth and precede the development of an upper airway obstruction. We identified that in this rodent model, no single feature appeared to predict upper airway obstruction, but the sum of those features resulted in a reduced breathing frequency, apneas and overall reduced oxygen consumption. Metabolomics analysis of serum from peripheral blood identified increased levels of hydroxyproline, a metabolite upregulated under hypoxic conditions. As this model recapitulates many features observed in OSA, it offers unique opportunities for studying how upper airway obstruction affects breathing physiology and leads to systemic morbidities.

中文翻译：

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Bmp7的神经7特异性缺失导致面中发育不全，鼻气道阻塞和呼吸模型障碍阻塞性睡眠呼吸暂停。

小儿阻塞性呼吸暂停（OSA）是一种相对常见的与睡眠有关的呼吸障碍（SRBD），影响大约1-5％的儿童，通常是由于解剖阻塞和/或鼻和/或咽气道塌陷引起的。导致的睡眠中断和间歇性缺氧导致各种全身性疾病。目前尚无法仅通过颅面特征来预测OSA的发展，如果上呼吸道阻塞促进了中面生长的减少，则仍存在争议。目前，尚无啮齿类动物模型可以概括颅面异常和上呼吸道阻塞的发生，以解决这些问题。在这里，我们描述了具有神经mp特定缺失的Bmp7（Bmp7 ^ncko）表现为较短，更尖锐的颅底，中面发育不全，鼻中隔偏曲，鼻甲肿胀和分支缺损以及鼻气道阻塞。有趣的是，这些颅面特征中的一些在出生后在快速的中面生长时期发展，并在上呼吸道阻塞发展之前发展。我们确定，在这种啮齿动物模型中，似乎没有单个特征可以预测上呼吸道阻塞，但是这些特征的总和导致呼吸频率降低，呼吸暂停和总体氧气消耗减少。外周血血清的代谢组学分析确定了羟脯氨酸水平升高，这是在缺氧条件下上调的代谢产物。由于该模型概括了OSA中观察到的许多功能，