Decreased lung compliance and air trapping in heterozygous SP-B-deficient mice.
Genetic ablation of the murine SP-B gene in transgenic mice caused lethal perinatal respiratory distress in homozygous offspring, whereas heterozygous SP-B (+/-) mice survived postnatally. In adult SP-B(+/-) mice, surfactant protein B mRNA and the alveolar lavage SP-B protein were reduced by 50% compared with wild-type littermates, consistent with the inactivation of a single SP-B allele. Expression of SP-A, SP-C, and SP-D proteins was not affected in SP-B(+/-) mice. Heterozygous SP-B(+/-) mice reached maturity in numbers expected by Mendelian inheritance of a recessive gene. Lung morphology and both intracellular and extracellular phospholipid pool size and composition were unaltered in the SP-B(+/-) mice. Despite normal survival, pulmonary function studies demonstrated a consistent decrease in lung compliance in SP-B(+/-) mice. Abnormalities of inflation/deflation curves demonstrated airway collapse at low deflation pressures. Residual volumes were increased in the SP-B(+/-) mice. In summary, SP-B mRNA and SP-B protein were reduced by 50% in SP-B(+/-) mice, resulting in abnormalities of lung compliance and air trapping, suggesting a potential susceptibility to pulmonary dysfunction associated with SP-B deficiency.
Clark
J C
JC
Division of Neonatology, Children's Hospital Medical Center, Cincinnati, Ohio 45229-3039, USA.
Weaver
T E
TE
Iwamoto
H S
HS
Ikegami
M
M
Jobe
A H
AH
Hull
W M
WM
Whitsett
J A
JA
D000818:Animals; D005260:Female; D018390:Gene Targeting; D006579:Heterozygote; D008168:Lung / Q000033:anatomy & histology / Q000378:metabolism / Q000502:physiology*; D008170:Lung Compliance; D008176:Lung Volume Measurements; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D010743:Phospholipids / Q000032:analysis; D011510:Proteolipids / Q000235:genetics / Q000378:metabolism*; D011650:Pulmonary Alveoli / Q000378:metabolism; D011663:Pulmonary Surfactants / Q000737:chemistry / Q000172:deficiency* / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D015656:Respiratory Mechanics
D010743:Phospholipids; D011510:Proteolipids; D011663:Pulmonary Surfactants; D012333:RNA, Messenger