Phenotypes Associated with This Genotype

Genotype
MGI:3605476

• Allelic Composition: Tg(Scgb1a1-Scnn1b)6608Bouc/0
• Genetic Background: involves: C3H * C57BL/6

• ♀: phenotype observed in females
• ♂: phenotype observed in males
• N: normal phenotype

mortality/aging

postnatal lethality ( J:91139 )

• 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

abnormal respiratory mucosa goblet cell morphology ( J:91139 )

• airway epithelia of adult transgenic mice exhibit goblet cell metaplasia

abnormal respiratory system physiology ( J:91139 )

• increased airway absorption of Na⁺ is demonstrated by elevation of basal and amiloride-sensitive short-circuit currents (I_sc) 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 wild-type levels

bronchitis ( J:91139 )

• 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

abnormal mucociliary clearance ( J:91139 )

• 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 wild-type mice, transgenic mice retained a significant bacterial burden

respiratory distress ( J:91139 )

• early deaths of transgenic mice result from asphyxia due to severe airway obstruction, evidenced by frequent observation of intercostal and subdiaphragmatic retractions

immune system

bronchitis ( J:91139 )

• 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		DO ID	OMIM ID(s)	Ref(s)
cystic fibrosis		DOID:1485	OMIM:219700	J:91139