Targeted disruption of the surfactant protein B gene disrupts surfactant homeostasis, causing respiratory failure in newborn mice.
Surfactant protein B (SP-B) is an 8.7-kDa, hydrophobic protein that enhances the spreading and stability of surfactant phospholipids in the alveolus. To further assess the role of SP-B in lung function, the SP-B gene was disrupted by homologous recombination in murine mouse embryonic stem cells. Mice with a single mutated SP-B allele (+/-) were unaffected, whereas homozygous SP-B -/- offspring died of respiratory failure immediately after birth. Lungs of SP-B -/- mice developed normally but remained atelectatic in spite of postnatal respiratory efforts. SP-B protein and mRNA were undetectable and tubular myelin figures were lacking in SP-B -/- mice. Type II cells of SP-B -/- mice contained no fully formed lamellar bodies. While the abundance of SP-A and SP-C mRNAs was not altered, an aberrant form of pro-SP-C, 8.5 kDa, was detected, and fully processed SP-C peptide was markedly decreased in lung homogenates of SP-B -/- mice. Ablation of the SP-B gene disrupts the routing, storage, and function of surfactant phospholipids and proteins, causing respiratory failure at birth.
Clark
J C
JC
Division of Pulmonary Biology, Children's Hospital Medical Center, Cincinnati, OH 45229-3039, USA.
Wert
S E
SE
Bachurski
C J
CJ
Stahlman
M T
MT
Stripp
B R
BR
Weaver
T E
TE
Whitsett
J A
JA
D000818:Animals; D000831:Animals, Newborn; D004622:Embryo, Mammalian; D004848:Epithelium / Q000473:pathology / Q000648:ultrastructure; D005822:Genetic Vectors; D015698:Genomic Library; D006706:Homeostasis; D006720:Homozygote; D006801:Humans; D008168:Lung / Q000473:pathology / Q000648:ultrastructure; D051379:Mice; D008822:Mice, Transgenic; D008854:Microscopy, Electron; D016296:Mutagenesis; D011510:Proteolipids / Q000096:biosynthesis / Q000235:genetics* / Q000502:physiology*; D011650:Pulmonary Alveoli / Q000473:pathology / Q000648:ultrastructure; D011663:Pulmonary Surfactants / Q000096:biosynthesis / Q000235:genetics* / Q000502:physiology*; D012333:RNA, Messenger / Q000032:analysis / Q000096:biosynthesis; D011994:Recombinant Proteins / Q000096:biosynthesis / Q000378:metabolism; D012016:Reference Values; D012131:Respiratory Insufficiency / Q000235:genetics / Q000473:pathology / Q000503:physiopathology*; D015183:Restriction Mapping; D013234:Stem Cells
D011510:Proteolipids; D011663:Pulmonary Surfactants; D012333:RNA, Messenger; D011994:Recombinant Proteins