Lethal Lung diesase (LAMP3)

Pulmonary surfactant is a mixture of lipids and proteins that form the thin surface lining film in the alveolus (the gas exchanging components of the lungs). The surfactant reduces the surface tension and therefore prevents the alveoli from collapsing at the end of expiration. Synthesis of the surfactant occurs in special cytoplasmic organelles, the so-called lamellar bodies, within the alveolar epithelial type II cells (AECII). After the synthesis, the lamellar bodies secrete the surfactant into the alveolar space.
In the breed Airedale Terrier, a variant in the LAMP3 gene, which encodes for a membrane protein of the lamellar bodies, has been found to induce a severe lung disease. The lamellar bodies are not able to develop completely which subsequently influences the synthesis of the surfactant. Homozygous affected puppies show a lethal hypoxic respiratory distress and failure within the first days or weeks of life. Typical symptoms are lethargy already at birth, the puppies refuse to suckle and develop dyspnea or tachypnea so that they usually have to be euthanized. The lungs of affected puppies have been found to be edematous, congested and appeared poorly aerated, sometimes with a rubbery texture.
As the screening of a lot of Airedale Terrier dogs for the described variant, a six-year-old female dog has been found to be genetically homozygous defected but according to the owner never showed any signs of respiratory disease. This suggests that there might be an unknown protective variant causing an incomplete penetrance of this lethal lung disease.