Mouse Genome Informatics
tg1
    Tg(Scgb1a1-Scnn1b)6608Bouc/0
involves: C3H * C57BL/6
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
mortality/aging
• although transgenic animals are born at the expected Mendelian ratios, 50% of transgenic mice of both sexes die from the first days of postnatal life through 4 weeks of age

respiratory system
• airway epithelia of adult transgenic mice exhibit goblet cell metaplasia
• increased airway absorption of Na+ is demonstrated by elevation of basal and amiloride-sensitive short-circuit currents (Isc) across freshly excised adult and neonatal tracheal tissue of transgenic mice over those of nontransgenic littermates; in contrast, both forskolin and UTP fail to increase chloride channel activation in amiloride pretreated transgenic tracheae above wildtype levels
• histopathologic examination of the lungs reveals evidence of chronic bronchitis, the lumina of conducting airways populated with macrophages and neutrophils; however, the submucosa contain few inflammatory cells
• bronchoalveolar lavage (BAL) fluid and lung homogenates of adult, but not neonatal, transgenic mice contain significantly higher levels of macrophage inflammatory protein 2 (MIP-2) and KC than do those of nontransgenic littermates
• lung histology of all transgenic mice is normal at birth, but those that die early exhibit severe obstruction of small and large airways by mucus plaques and plugs; those euthanized after 4 weeks have less severe mucus obstruction with dilation of airspaces distal to blockages
• airway mucus of transgenic mice is significantly more concentrated than that of nontransgenic littermates; electron and light microscopy reveal adhesion of mucus to airway epithelia and reduction of periciliary liquid (PCL) height in tracheae and bronchi of transgenic mice
• the rate of clearance of a fluorescent dye demonstrates slower in vitro mucus transport in the lower airways of transgenic mice than of nontransgenic littermates, and whereas intratracheally instilled Haemophilus influenzae or Pseudomonas aeruginosa were almost completely cleared within 3 days from the lungs of wildtype mice, transgenic mice retained a significant bacterial burden
• early deaths of transgenic mice result from asphyxia due to severe airway obstruction, evidenced by frequent observation of intercostal and subdiaphragmatic retractions

immune system
• histopathologic examination of the lungs reveals evidence of chronic bronchitis, the lumina of conducting airways populated with macrophages and neutrophils; however, the submucosa contain few inflammatory cells
• bronchoalveolar lavage (BAL) fluid and lung homogenates of adult, but not neonatal, transgenic mice contain significantly higher levels of macrophage inflammatory protein 2 (MIP-2) and KC than do those of nontransgenic littermates

Mouse Models of Human Disease
OMIM IDRef(s)
Cystic Fibrosis; CF 219700 J:91139