Neonatal lethality in mice deficient in XCE, a novel member of the endothelin-converting enzyme and neutral endopeptidase family.
XCE, a new member of the endothelin-converting enzyme and neutral endopeptidase family, is preferentially expressed in specific areas of the central nervous system including spinal chord and medulla. To elucidate the importance and function of XCE, we disrupted its gene in mouse embryonic stem cells by homologous recombination and created mice deficient in XCE. The resulting phenotype is characterized by neonatal lethality. All XCE -/- homozygous mice died of respiratory failure shortly after birth, and in most cases their lungs were never ventilated. Apart from the atelectasis, anatomical and histological examinations of embryonic day 18.5 XCE -/- embryos and newborn homozygotes did not reveal any obvious abnormalities in organs and tissues. Malformations that are related to the knock-out were also not found in the skeletons of XCE -/- mice. In addition, XCE knock-out animals showed no deficiency of pulmonary surfactant proteins and had normal heart beat frequencies. Taken together, our results demonstrate that XCE is an essential gene. The phenotype of the XCE-deficient mice together with the central nervous system-specific expression further suggest that XCE may play a vital role in the control of respiration.
Preclinical Cardiovascular Research, F. Hoffmann-La Roche Ltd., Pharma Division, Grenzacherstrasse 124, 4070 Basel, Switzerland.
A
A
Schweizer
O
O
Valdenaire
A
A
Köster
Y
Y
Lang
G
G
Schmitt
B
B
Lenz
H
H
Bluethmann
J
J
Rohrer
D000818:Animals; D000831:Animals, Newborn; D001483:Base Sequence; D001842:Bone and Bones / Q000002:abnormalities; D017931:DNA Primers; D004622:Embryo, Mammalian / Q000166:cytology; D005260:Female; D005804:Genes, Lethal; D006339:Heart Rate; D006720:Homozygote; D008168:Lung / Q000473:pathology; D008297:Male; D008666:Metalloendopeptidases / Q000235:genetics*; D051379:Mice; D018345:Mice, Knockout; D011663:Pulmonary Surfactants / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics; D013234:Stem Cells / Q000378:metabolism
D017931:DNA Primers; D011663:Pulmonary Surfactants; D012333:RNA, Messenger; C120591:Ecel1 protein, mouse; D008666:Metalloendopeptidases