Expression of Sleep Disordered Breathing in Inbred

Rubin, Arnon

Abstract

Sleep disordered Breathing (SDB) is a prevalent condition affecting 2-4% of the adult population in the United States. Obstructive Sleep Apnea is the most common form of SDB, and is characterized by recurrent occlusion of the upper airway during sleep leading to oxyhemoglobin desaturation and periodic arousal from sleep. The severity of SDB can vary markedly in individuals despite similar physical characteristics. Respiratory control mechanisms such as hypoxic sensitivity may play an important role in determining such variability. Our approach is utilize specific inbred mouse strains that exhibit markedly different ventilatory responsiveness. Based on our Preliminary Data, we propose that in inbred mice, hypoxic ventilatory sensitivity affects the expression of sleep disordered breathing.In the proposed studies, we will, first, fully characterize respiratory control mechanisms across sleep/wake states in two inbred mouse strains that represent the extremes of low (A/J) and high (DBA/2J) ventilatory responses to hypoxia during wakefulness (Specific Aim #1). Second, we will utilize a novel model of SDB in the mouse to determine if genetic differences in respiratory control in the A/J and DBA/2J strains result in differential expression of SDB severity (Specific Aim #2 and 3). We anticipate these studies will provide unique insights not possible in human studies, and lead to a better understanding of how genetic determinants of respiratory control contribute to the expression of SDB.