RT Journal Article
SR Electronic
T1 DSCAM Deficiency Causes Loss of Pre-Inspiratory Neuron Synchroneity and Perinatal Death
JF The Journal of Neuroscience
JO J. Neurosci.
FD Society for Neuroscience
SP 2984
OP 2996
DO 10.1523/JNEUROSCI.3624-08.2009
VO 29
IS 9
A1 Kenji Amano
A1 Morimitsu Fujii
A1 Satoru Arata
A1 Takuro Tojima
A1 Masaharu Ogawa
A1 Noriyuki Morita
A1 Atsushi Shimohata
A1 Teiichi Furuichi
A1 Shigeyoshi Itohara
A1 Hiroyuki Kamiguchi
A1 Julie R. Korenberg
A1 Akiko Arata
A1 Kazuhiro Yamakawa
YR 2009
UL http://www.jneurosci.org/content/29/9/2984.abstract
AB Down syndrome cell adhesion molecule (DSCAM) is a neural adhesion molecule that plays diverse roles in neural development. We disrupted the Dscam locus in mice and found that the null mutants (Dscam−/−) died within 24 h after birth. Whole-body plethysmography showed irregular respiration and lower ventilatory response to hypercapnia in the null mutants. Furthermore, a medulla–spinal cord preparation of Dscam−/− mice showed that the C4 ventral root activity, which drives diaphragm contraction for inspiration, had an irregular rhythm with frequent apneas. Optical imaging of the preparation using voltage-sensitive dye revealed that the pre-inspiratory neurons located in the rostral ventrolateral medulla and belonging to the rhythm generator for respiration, lost their synchroneity in Dscam−/− mice. Dscam+/− mice, which survived to adulthood without any overt abnormalities, also showed irregular respiration but milder than Dscam−/− mice. These results suggest that DSCAM plays a critical role in central respiratory regulation in a dosage-dependent manner.