Phenotypes Associated with This Genotype

Genotype
MGI:5473699

• Allelic Composition: Adora2a^tm1Jfc/Adora2a^tm1Jfc
• Genetic Background: B6.129S4-Adora2a^tm1Jfc

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

cardiovascular system

abnormal pulmonary artery morphology ( J:194389 )

• 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

abnormal lung vasculature morphology ( J:194389 )

• 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

vascular smooth muscle hypertrophy ( J:194389 )

• pulmonary artery wall exhibits increased smooth muscle cell hypertorphy

heart right ventricle hypertrophy ( J:194389 )

• 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

increased right ventricle systolic pressure ( J:194389 )

• 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

pulmonary hypertension ( J:194389 )

• 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

vascular smooth muscle hypertrophy ( J:194389 )

• pulmonary artery wall exhibits increased smooth muscle cell hypertorphy

heart right ventricle hypertrophy ( J:194389 )

• 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

respiratory system

abnormal lung vasculature morphology ( J:194389 )

• 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

growth/size/body

heart right ventricle hypertrophy ( J:194389 )

• 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

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
primary pulmonary hypertension		DOID:14557	OMIM:178600 OMIM:265400 OMIM:615342 OMIM:615343 OMIM:615344	J:194389