LAMP3 deficiency affects surfactant homeostasis in mice

PLoS Genet. 2021 Jun 23;17(6):e1009619. doi: 10.1371/journal.pgen.1009619. eCollection 2021 Jun.


Lysosome-associated membrane glycoprotein 3 (LAMP3) is a type I transmembrane protein of the LAMP protein family with a cell-type-specific expression in alveolar type II cells in mice and hitherto unknown function. In type II pneumocytes, LAMP3 is localized in lamellar bodies, secretory organelles releasing pulmonary surfactant into the extracellular space to lower surface tension at the air/liquid interface. The physiological function of LAMP3, however, remains enigmatic. We generated Lamp3 knockout mice by CRISPR/Cas9. LAMP3 deficient mice are viable with an average life span and display regular lung function under basal conditions. The levels of a major hydrophobic protein component of pulmonary surfactant, SP-C, are strongly increased in the lung of Lamp3 knockout mice, and the lipid composition of the bronchoalveolar lavage shows mild but significant changes, resulting in alterations in surfactant functionality. In ovalbumin-induced experimental allergic asthma, the changes in lipid composition are aggravated, and LAMP3-deficient mice exert an increased airway resistance. Our data suggest a critical role of LAMP3 in the regulation of pulmonary surfactant homeostasis and normal lung function.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Airway Resistance
  • Alveolar Epithelial Cells / metabolism*
  • Alveolar Epithelial Cells / pathology
  • Animals
  • Asthma / chemically induced
  • Asthma / genetics*
  • Asthma / metabolism
  • Asthma / pathology
  • Bronchoalveolar Lavage Fluid
  • Disease Models, Animal
  • Female
  • Gene Editing / methods
  • Gene Expression Regulation
  • Homeostasis / genetics*
  • Lipidomics
  • Lung / metabolism
  • Lung / pathology
  • Lysosomal-Associated Membrane Protein 3 / deficiency
  • Lysosomal-Associated Membrane Protein 3 / genetics*
  • Mice
  • Mice, Knockout
  • Ovalbumin / administration & dosage
  • Protein Isoforms / genetics
  • Protein Isoforms / metabolism
  • Pulmonary Alveoli / metabolism
  • Pulmonary Alveoli / pathology
  • Pulmonary Surfactant-Associated Protein C / genetics*
  • Pulmonary Surfactant-Associated Protein C / metabolism
  • Pulmonary Surfactants / metabolism*
  • Respiratory Function Tests
  • Signal Transduction


  • Lysosomal-Associated Membrane Protein 3
  • Protein Isoforms
  • Pulmonary Surfactant-Associated Protein C
  • Pulmonary Surfactants
  • Sftpc protein, mouse
  • Ovalbumin

Grants and funding

RS’s work was supported by funding of the Ministry of Education, Youth and Sports to the Czech Centre for Phenogenomics (LM2018126) and by the Institute of Molecular Genetics of the Czech Academy of Sciences (RVO 68378050). Research in DS’s lab was supported by Lipidomics Informatics for Life Science (LIFS) of the German Network for Bioinformatics Infrastructure (de.NBI, BMBF). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.