抄録
DSCAM1 on human chromosome 21q22 is a neural adhesion molecule that plays diverse roles in the neural development. We disrupted the Dscam1 locus in mouse and found that the Dscam1−/− mice died within 24 hours after birth. Whole body plethysmography of the mice showed irregular respiration. Further, inspiratory activity of the C4 ventral root that drives diaphragm, assessed in a medulla-spinal cord preparation of Dscam1−/− mice, also showed irregular rhythm with frequent apnea. In Dscam1−/− mice, optical imaging of this preparation by using voltage-sensitive dye revealed that the synchroneity of pre-inspiratory (Pre-I) neuron activity in para-facial respiratory group (pFRG) as a respiratory rhythm generator was lost, while that of inspiratory neuron activity in pre-Botzinger complex as a pattern generator was preserved in rostral ventrolateral medulla (RVLM). In the immunohistochemical analysis with SMI311, that the marker for neuronal soma and dendrites, the number of SMI311-positive neurons was increased at dorsolateral facial nucleus. The VII nerve root activities that included Pre-I burst activity were decreased in Dscam1−/− mice. According to the test of respiratory network induced by RVLM stimulation, bilateral neural connections were disrupted. These results suggest that the deficiency of Dscam1 selectively depressed Pre-I neuron network and its deficiency causes congenital central hypoventilation. [J Physiol Sci. 2008;58 Suppl:S117]
