DSCAM deficiency causes loss of pre-inspiratory neuron synchroneity and perinatal death.
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.
Amano
Kenji
K
Laboratory for Neurogenetics, RIKEN Brain Science Institute, Wako-shi, Saitama 351-0198, Japan.
Fujii
Morimitsu
M
Arata
Satoru
S
Tojima
Takuro
T
Ogawa
Masaharu
M
Morita
Noriyuki
N
Shimohata
Atsushi
A
Furuichi
Teiichi
T
Itohara
Shigeyoshi
S
Kamiguchi
Hiroyuki
H
Korenberg
Julie R
JR
Arata
Akiko
A
Yamakawa
Kazuhiro
K
D000818:Animals; D000831:Animals, Newborn; D015152:Blotting, Northern; D015815:Cell Adhesion Molecules / Q000235:genetics* / Q000502:physiology*; D003643:Death; D004594:Electrophysiology; D018274:Electroporation; D005727:Ganglia, Spinal / Q000166:cytology / Q000502:physiology; D006339:Heart Rate / Q000502:physiology; D006935:Hypercapnia / Q000473:pathology / Q000503:physiopathology; D017403:In Situ Hybridization; D008526:Medulla Oblongata / Q000002:abnormalities; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D016501:Neurites / Q000502:physiology; D009474:Neurons / Q000502:physiology*; D010993:Plethysmography, Whole Body; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D015656:Respiratory Mechanics / Q000502:physiology; D012137:Respiratory System / Q000294:innervation*
D015815:Cell Adhesion Molecules; C491735:Dscam protein, mouse; D012333:RNA, Messenger