Cis-acting sequences from a human surfactant protein gene confer pulmonary-specific gene expression in transgenic mice

Journal Article · Wed Aug 01 00:00:00 EDT 1990 · Proceedings of the National Academy of Sciences of the United States of America; (USA)

DOI:https://doi.org/10.1073/pnas.87.16.6122· OSTI ID:5841824

Korfhagen, T R; Glasser, S W; Wert, S E; Bruno, M D; Daugherty, C C; McNeish, J D; Stock, J L; Potter, S S; Whitsett, J A ^[1]

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1. Cincinnati College of Medicine, OH (USA)

Pulmonary surfactant is produced in late gestation by developing type II epithelial cells lining the alveolar epithelium of the lung. Lack of surfactant at birth is associated with respiratory distress syndrome in premature infants. Surfactant protein C (SP-C) is a highly hydrophobic peptide isolated from pulmonary tissue that enhances the biophysical activity of surfactant phospholipids. Like surfactant phospholipid, SP-C is produced by epithelial cells in the distal respiratory epithelium, and its expression increases during the latter part of gestation. A chimeric gene containing 3.6 kilobases of the promoter and 5{prime}-flanking sequences of the human SP-C gene was used to express diphtheria toxin A. The SP-C-diphtheria toxin A fusion gene was injected into fertilized mouse eggs to produce transgenic mice. Affected mice developed respiratory failure in the immediate postnatal period. Morphologic analysis of lungs from affected pups showed variable but severe cellular injury confined to pulmonary tissues. Ultrastructural changes consistent with cell death and injury were prominent in the distal respiratory epithelium. Proximal components of the tracheobronchial tree were not severely affected. Transgenic animals were of normal size at birth, and structural abnormalities were not detected in nonpulmonary tissues. Lung-specific diphtheria toxin A expression controlled by the human SP-C gene injured type II epithelial cells and caused extensive necrosis of the distal respiratory epithelium. The absence of type I epithelial cells in the most severely affected transgenic animals supports the concept that developing type II cells serve as precursors to type I epithelial cells.

• OSTI ID: 5841824
• Journal Information: Proceedings of the National Academy of Sciences of the United States of America; (USA), Vol. 87:16; ISSN 0027-8424
• Country of Publication: United States
• Language: English

Related Subjects

59 BASIC BIOLOGICAL SCIENCES
GENES
DNA SEQUENCING
SURFACTANTS
PHYSIOLOGY
DIPHTHERIA
EPITHELIUM
ESCHERICHIA COLI
GENE REPRESSORS
LUNGS
PHOSPHOLIPIDS
TOXINS
ULTRASTRUCTURAL CHANGES
ANIMAL TISSUES
ANTIGENS
BACTERIA
BACTERIAL DISEASES
BODY
DISEASES
ESTERS
INFECTIOUS DISEASES
LIPIDS
MATERIALS
MICROORGANISMS
MORPHOLOGICAL CHANGES
NUCLEOPROTEINS
ORGANIC COMPOUNDS
ORGANIC PHOSPHORUS COMPOUNDS
ORGANS
PROTEINS
RESPIRATORY SYSTEM
STRUCTURAL CHEMICAL ANALYSIS
TISSUES
TOXIC MATERIALS
550200* - Biochemistry