The pallid mouse. A model of genetic alpha 1-antitrypsin deficiency.
Lab Invest
; 68(2): 233-41, 1993 Feb.
Article
en En
| MEDLINE
| ID: mdl-8441253
ABSTRACT
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. EXPERIMENTALDESIGN:
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.
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Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Enfisema Pulmonar
/
Deficiencia de alfa 1-Antitripsina
/
Modelos Animales de Enfermedad
Límite:
Animals
Idioma:
En
Revista:
Lab Invest
Año:
1993
Tipo del documento:
Article
País de afiliación:
Alemania