Mouse Genome Informatics
tg
    Tg(Scgb1a1-IL6)9Flv/0
involves: C57BL/6 * CBA
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
       
growth/size
• 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
• 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
• mice exhibit pulmonary vascular remodeling as indicated by increased muscularization of the proximal arterial tree and formation of occlusive neointimal angioproliferative lesions
• 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)
• 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
• 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
• 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
• mice exhibit pulmonary vascular remodeling as indicated by increased muscularization of the proximal arterial tree and formation of occlusive neointimal angioproliferative lesions
• 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
• 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

Mouse Models of Human Disease
OMIM IDRef(s)
Pulmonary Hypertension, Primary, 1; PPH1 178600 J:156430