Mouse Genome Informatics
hm
    Adora2atm1Jfc/Adora2atm1Jfc
B6.129S4-Adora2atm1Jfc
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
       
cardiovascular system
• cell proliferation is increased in all major cell types across entire pulmonary arterial walls, including smooth muscle, endothelium cells and fibroblasts compared to wild-type mice
• pulmonary arteries exhibit swelling and hypertrophy of endothelial and smooth muscle cells, with abundance of cytoplasm and an increase in intracytoplasmic vesicles
• pulmonary artery endothelium contains more Weibel-Palade bodies than in wild-type, indicating activation of endothelial cells
• cytoplasm of pulmonary artery smooth muscle cells contains numerous filaments and dense bodies, indicating activation of smooth muscle cells
• mutants exhibit enhanced hyperplasia of pulmonary artery fibroblasts, as indicated by an increase in fibroblasts seen outside the external elastic laminae and more clustered collagaen fibers deposition in adventitia pulmonary arterial walls
• mutants exhibit hypertrophy of pulmonary resistance vessels with increased wall thickness and area
• mice exhibit evidence of pulmonary vascular remodeling, showing fibroblast, smooth muscle and endothelium cell hypertrophy
• however, mutants do not exhibit pulmonary edema, lung inflammation, fibrosis or thickening of the alveolar septa
• pulmonary artery wall exhibits increased smooth muscle cell hypertorphy
• the mean Fulton index (ratio of right ventricle over left ventricle plus septum) is higher in mutants than wild-type mice at 14-16 weeks of age, indicating hypertrophic right ventricles
• mice exhibit a 44.8% increase in right ventricular systolic pressure at 14-16 weeks of age
• however, mean systolic blood pressure and heart rate are normal
• following chronic exposure to hypoxia, mutants show an exacerbated elevation in right ventricular systolic pressure
• mice develop pulmonary arterial hypertension without affecting systemic circulation or heart rate
• following chronic exposure to hypoxia, mutants show exacerbated elevation in right ventricular systolic pressure, hypertrophy of pulmonary resistance vessels, and increased cell proliferation in pulmonary resistance vessels compared to wild-type mice, indicating a further increase in pulmonary hypertension under hypoxic conditions
• however, mutants do not show any features of hypertensive nephropathy

muscle
• pulmonary artery wall exhibits increased smooth muscle cell hypertorphy

respiratory system
• mutants exhibit hypertrophy of pulmonary resistance vessels with increased wall thickness and area
• mice exhibit evidence of pulmonary vascular remodeling, showing fibroblast, smooth muscle and endothelium cell hypertrophy
• however, mutants do not exhibit pulmonary edema, lung inflammation, fibrosis or thickening of the alveolar septa

Mouse Models of Human Disease
OMIM IDRef(s)
Pulmonary Hypertension, Primary, 1; PPH1 178600 J:194389