Phenotypes Associated with This Genotype

Genotype
MGI:5474461

• Allelic Composition: Tg(Scgb1a1-IL6)9Flv/0
• Genetic Background: involves: C57BL/6 * CBA

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

growth/size/body

heart right ventricle hypertrophy ( J:156430 )

• ratio of right ventricle to left ventricle plus septum weight and absolute right ventricle weight are increased under normoxic conditions indicating right ventricle hypertrophy

• hypoxia results in an even greater right ventricle hypertrophy, however no change in ventricular wall thickness is seen

decreased body weight ( J:128762 )

• while mutants are normal weight when young, with age, they exhibit stunted growth and weigh less than wild-type mice

• females show a lower weight at 11 weeks of age, while males show a difference at 16 weeks of age

immune system

lung inflammation ( J:128762 , J:156430 )

• mononuclear cell infiltrate is seen adjacent to large and mid-sized airways indicating development of a chronic peribronchial inflammatory response (J:128762)

• cells are predominately CD4+ cells, MHC class II+ cells, and B220+ cells (J:128762)

• despite airway inflammation, mutants show normal basal airway resistance (J:128762)

• the number of periarteriolar lymphocytes, predominately T cells, are increased within the pulmonary vascular bed (J:156430)

respiratory system

abnormal lung vasculature morphology ( J:156430 )

• mice exhibit pulmonary vascular remodeling as indicated by increased muscularization of the proximal arterial tree and formation of occlusive neointimal angioproliferative lesions

lung inflammation ( J:128762 , J:156430 )

• mononuclear cell infiltrate is seen adjacent to large and mid-sized airways indicating development of a chronic peribronchial inflammatory response (J:128762)

• cells are predominately CD4+ cells, MHC class II+ cells, and B220+ cells (J:128762)

• despite airway inflammation, mutants show normal basal airway resistance (J:128762)

• the number of periarteriolar lymphocytes, predominately T cells, are increased within the pulmonary vascular bed (J:156430)

abnormal respiratory mechanics ( J:128762 )

• although mutants exhibit a normal baseline respiratory system resistance, they require a higher dose of methacholine to produce a 100% increase in respiratory system resistance compared to wild-type mice indicating decreased susceptibility to methacholine-induced bronchoconstriction

cardiovascular system

abnormal pulmonary artery morphology ( J:156430 )

• main pulmonary artery branches exhibit an increase in the number of elastic lamina that is further increased following hypoxia

• medial wall thickness of the main pulmonary artery branches are increased under normoxic conditions but do not change in hypoxic mutants

• distal acinar arterioles show increased muscularization under normoxic conditions and become more thickly muscularized in hypoxia

• an increase in proliferation within the intimal wall of arterioles is seen both under normoxic and hypoxic conditions

• the number of arteries per 100 alveoli are reduced more in mutants than wild-type mice under hypoxic conditions

artery occlusion ( J:156430 )

• mutants exhibit arteriolar neointimal occlusive lesions, with arteriolar lumens partially (27%) or completely (4%) occluded in the lungs under normoxic conditions

• hypoxia increases the number of partially (55%) or completely (14%) occluded arterioles compared to partial occlusion (3%) in wild-type mice

• arteriole walls are thickened by multiple layers of pulmonary artery endothelial cells either forming smooth and thick concentric occlusive lesions or plexogenic-like occlusive lesions

abnormal lung vasculature morphology ( J:156430 )

• mice exhibit pulmonary vascular remodeling as indicated by increased muscularization of the proximal arterial tree and formation of occlusive neointimal angioproliferative lesions

heart right ventricle hypertrophy ( J:156430 )

• ratio of right ventricle to left ventricle plus septum weight and absolute right ventricle weight are increased under normoxic conditions indicating right ventricle hypertrophy

• hypoxia results in an even greater right ventricle hypertrophy, however no change in ventricular wall thickness is seen

increased right ventricle systolic pressure ( J:156430 )

• mutants exhibit elevated right ventricular systolic pressure under normoxic conditions

• mutants exhibit almost 2.6 times higher levels of right ventricular systolic pressure after 3 weeks of exposure to hyoxia (10% oxygen) compared to wild-type mice

muscle

heart right ventricle hypertrophy ( J:156430 )

• ratio of right ventricle to left ventricle plus septum weight and absolute right ventricle weight are increased under normoxic conditions indicating right ventricle hypertrophy

• hypoxia results in an even greater right ventricle hypertrophy, however no change in ventricular wall thickness is seen

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:156430