Naturally occurring mice strains that develop airspace enlargement and emphysema
| Mouse | Genetic/physiological defect | Phenotype | Lung phenotype | Reference |
|---|---|---|---|---|
| CTL=cytotoxic T lymphocytes; NK=natural killer cells. | ||||
| Tight skin (Tsk+/–) | • Duplication of fibrillin 1 (Fbn-1), main component of 10–12 nm extracellular microfibrils (causes Marfan’s syndrome in man) | • Tight skins, hyperplasia of subcutaneous connective tissues, ↑ growth of cartilage and bone, small tendons, hyperplasia of tendon sheaths | • Panlobular emphysema develops after 4 days of life | 58– 63 |
| • Possible dominant negative effect of Tsk Fbn-1 by incorporation into microfibrils, rendering them susceptible to proteolysis | • Emphysema is preceded by a low level macrophage-neutrophil alveolitis | |||
| Beige (Bg) | • 5 kb deletion in Lyst (causes Chediak-Higashi syndrome in man) | • Dilution of coat colour, recurrent infections, giant granules | • Normal at birth, abnormal neonatal alveolarisation | 60, 63– 65 |
| • Lysosomal missorting of proteins such as elastase, glucuronidase and cathepsin G | • Adult lungs: fewer alveoli, smooth terminal air ducts lacking the normal complement of alveolar struts | |||
| • Intracellular vesicle transport defect and generalised immunodeficiency in mice and humans (abnormal function of NK cells, CTL) | ||||
| Blotchy | • X-linked defective copper transport | • Aortic aneurysms, reduced skin tensile, develop osteoarthrosis | • Enlarged airspaces | 66– 68 |
| • Abnormal RNA splicing of the mouse homologue of copper ion transporting ATPase, Atp7A (Menke gene; Menkes disease in humans) | • Disruption of elastic fibres | |||
| • Impaired lysyl oxidase, abnormal collagen and elastin cross linking | ||||
| Pallid (Pa) | • 1 of 13 platelet storage pool deficiency mouse mutants | • Prolonged bleeding time, pigment dilution, kidney lysosomal enzyme elevation | • Progressive emphysema from 1 month | 60, 69– 71 |
| • Nonsense mutation at codon 69 in Pallidin which interacts with syntaxin 13: important in vesicle docking and fusion | • Serum α1-antitrypsin deficiency, abnormal otolith formation | • ↑ elastase, ↓ lung elastin | ||
| • Defect in organelle biosynthesis | • ↑ intracytoplasmic crystalloid inclusions related to collagen degradation in pulmonary macrophages | |||
| Osteopetrotic (Op/Op) | • Deficient in macrophage colony stimulating factor | • Osteopetrosis | • Young mice have reduced numbers of lung macrophages (which return to normal as they age) and emphysema | 72 |
| • Macrophages release more MMPs | ||||
| • BAL IL-3 is increased | ||||