Altered surfactant function and structure in SP-A gene targeted mice.
The surfactant protein A (SP-A) gene was disrupted by homologous recombination in embryonic stem cells that were used to generate homozygous SP-A-deficient mice. SP-A mRNA and protein were not detectable in the lungs of SP-A(-/-) mice, and perinatal survival of SP-A(-/-) mice was not altered compared with wild-type mice. Lung morphology, surfactant proteins B-D, lung tissue, alveolar phospholipid pool sizes and composition, and lung compliance in SP-A(-/-) mice were unaltered. At the highest concentration tested, surfactant from SP-A(-/-) mice produced the same surface tension as (+/+) mice. At lower concentrations, minimum surface tensions were higher for SP-A(-/-) mice. At the ultrastructural level, type II cell morphology was the same in SP-A(+/+) and (-/-) mice. While alveolar phospholipid pool sizes were unperturbed, tubular myelin figures were decreased in the lungs of SP-A(-/-) mice. A null mutation of the murine SP-A gene interferes with the formation of tubular myelin without detectably altering postnatal survival or pulmonary function.
Korfhagen
T R
TR
Children's Hospital Medical Center, Department of Pediatrics, Cincinnati, OH 45229-3039, USA.
Bruno
M D
MD
Ross
G F
GF
Huelsman
K M
KM
Ikegami
M
M
Jobe
A H
AH
Wert
S E
SE
Stripp
B R
BR
Morris
R E
RE
Glasser
S W
SW
Bachurski
C J
CJ
Iwamoto
H S
HS
Whitsett
J A
JA
D000818:Animals; D015139:Blotting, Southern; D018390:Gene Targeting; D005838:Genotype; D006023:Glycoproteins / Q000235:genetics / Q000502:physiology*; D051379:Mice; D016297:Mutagenesis, Site-Directed; D010743:Phospholipids / Q000032:analysis; D011510:Proteolipids / Q000235:genetics / Q000502:physiology*; D011650:Pulmonary Alveoli / Q000648:ultrastructure; D037662:Pulmonary Surfactant-Associated Protein A; D037661:Pulmonary Surfactant-Associated Proteins; D011663:Pulmonary Surfactants / Q000235:genetics / Q000502:physiology*; D012333:RNA, Messenger / Q000378:metabolism
D006023:Glycoproteins; D010743:Phospholipids; D011510:Proteolipids; D037662:Pulmonary Surfactant-Associated Protein A; D037661:Pulmonary Surfactant-Associated Proteins; D011663:Pulmonary Surfactants; D012333:RNA, Messenger