The pallid mouse. A model of genetic alpha 1-antitrypsin deficiency

Lab Invest. 1993 Feb;68(2):233-41.


Background: The current hypothesis of pulmonary emphysema is based on an alteration of the protease-antiprotease balance within the lower respiratory tract. This hypothesis derives largely from studies in emphysema patients with genetic deficiency in serum alpha 1-antitrypsin. In animals, naturally occurring deficiency in serum elastase inhibitory capacity associated with early development of emphysema has been reported in the tight-skin mouse. We describe here a mouse model of genetic deficiency of alpha 1-antitrypsin in which emphysema occurs late in life.

Experimental design: A genetic deficiency in serum alpha 1-antitrypsin was investigated in pallid mice, a strain with spontaneous occurring emphysema. Additionally, the possible pathogenetic role of an elastase-anti-elastase imbalance in pallid mice was investigated using molecular biologic, biochemical, histologic, ultrastructural, and immunoelectron microscopic methods.

Results: Pallid mice have markedly low levels of serum alpha 1-antitrypsin associated with a severe deficiency in serum elastase inhibitory capacity. However, they have normal alpha 1-antitrypsin mRNA levels in the liver. At ultrastructural examination, disruption of alveolar septa is first seen at 8 months of age. At histologic examination, some patchy areas of air-space enlargement with destruction of alveolar septa are seen from 12 months of age onward. These histologic changes are paralleled by a decrease in lung elastin content. The development of the pulmonary lesions is preceded by an alveolar elastolytic burden detected by an immunogold technique.

Conclusions: All these data suggest that the lung changes in pallid mice are the result of an elastolytic process due to a severe inborn deficiency of serum alpha 1-antitrypsin. This animal model reproduces important features of the human condition and may provide new insights into the pathogenesis of emphysema.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Base Sequence
  • Disease Models, Animal*
  • Elastin / analysis
  • Lung / chemistry
  • Lung / pathology
  • Lung / ultrastructure
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred C57BL
  • Microscopy, Electron
  • Microscopy, Immunoelectron
  • Molecular Sequence Data
  • Pancreatic Elastase / analysis
  • Pancreatic Elastase / antagonists & inhibitors
  • Pancreatic Elastase / immunology
  • Pulmonary Alveoli / ultrastructure
  • Pulmonary Emphysema / etiology*
  • Pulmonary Emphysema / pathology
  • alpha 1-Antitrypsin / genetics
  • alpha 1-Antitrypsin Deficiency*


  • alpha 1-Antitrypsin
  • Elastin
  • Pancreatic Elastase