Mouse Genome Informatics
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    Viptm1Clw/Viptm1Clw
involves: 129S/Sv * C57BL/6
Key:
phenotype observed in females
phenotype observed in males
N normal phenotype
behavior/neurological
• in constant darkness most (20/23) mutants have a significantly shorter period
• a few (3/23) mutants become arrhythmic immediately after the onset of constant darkness and 3 of the 20 that initially display short periods become arrhythmic over time
• at the onset of constant darkness mutants begin activity earlier than predicted from the previous light dark cycle and this onset is too early to be explained by the shorter circadian period
• mutants display 2 discrete bouts of activity when exposed to two 1 hour light pulses in a 24 hour period unlike controls which display a single bout of activity

cardiovascular system
• increase in proliferation of pulmonary medial smooth muscle cells
• males show an enlarged, thickened pulmonary artery and smaller branches with increased muscularization and narrowed lumen
• medial wall of pulmonary arteries is thicker and lumen is narrower resulting in numerous severely narrowed vessels that appear almost totally occluded
• males exhibit pulmonary vascular remodeling
• males treated with vasoactive intestinal peptide for 4 weeks show attenuation of vascular remodeling and right ventricle hypertrophy
• however, renal arteries do not show any evidence of vascular thickening
• males, but not females, exhibit moderate right ventricular hypertrophy as indicated by an increased ratio of right ventricle to left ventricle plus septum weight
• males treated with vasoactive intestinal peptide for 4 weeks show attenuation of vascular remodeling and right ventricle hypertrophy
• mean right ventricle systolic pressure is elevated in males at 40 and 48 weeks of age indicating development of moderate right ventricular hypertension
• right ventricular systolic pressure and right ventricle to left ventricle and septum weight ratio is increased in males indicating presence of moderately severe pulmonary arterial hypertension

immune system
• perivascular inflammatory cell infiltrates, predominantly mononuclear infiltrates, are seen around smaller pulmonary vessels and airways of males

mortality/aging
• increased mortality is seen in males, with mice starting to die at 6 months

respiratory system
• males exhibit pulmonary vascular remodeling
• males treated with vasoactive intestinal peptide for 4 weeks show attenuation of vascular remodeling and right ventricle hypertrophy
• however, renal arteries do not show any evidence of vascular thickening
• perivascular inflammatory cell infiltrates, predominantly mononuclear infiltrates, are seen around smaller pulmonary vessels and airways of males

Mouse Models of Human Disease
OMIM IDRef(s)
Pulmonary Hypertension, Primary, 1; PPH1 178600 J:132313