Mouse Genome Informatics
hm
    Hmox1tm1Mlee/Hmox1tm1Mlee
involves: 129S2/SvPas * BALB/c
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
       
mortality/aging
• all mice infected with Plasmodium chabaudi chabaudi die unlike control mice without an increase in parasitemia
• only ~20% of newborn homozygotes are obtained from heterozygote breedings, suggesting partial perinatal lethality
• at 3 weeks, only about 7% of homozygotes are obtained from heterozygote matings; surviving homozygotes appear grossly normal

cardiovascular system
• in response to chronic hypoxia (10% oxygen, 7 weeks), homozygotes display mononuclear inflammatory cell infiltration and extensive cardiomyocyte degeneration and death with focal calcification, characteristic of infarcts which are 1-2 weeks old
• in response to chronic hypoxia (10% oxygen, 7 weeks), homozygotes exhibit a greater increase in right ventricular weight relative to wild-type mice
• in response to chronic hypoxia (10% oxygen, 5-7 weeks), homozygotes show comparable increases in hematocrit values, pulmonary hypertension (right ventricular systolic pressure) and pulmonary vascular remodeling (peripheral muscularized vessels) relative to wild-type mice
• however, in response to chronic hypoxia (10% oxygen, 5 weeks), homozygotes exhibit increased right ventricular dilation relative to wild-type mice, with severe dilation noted at 7 weeks
• in response to chronic hypoxia (10% oxygen, 7 weeks), homozygotes exhibit increased perivascular fibrosis, with earlier collagen deposition and scar formation surrounding infarcted sites relative to wild-type mice
• in response to chronic hypoxia (10% oxygen, 7 weeks), homozygotes display increased cardiomyocyte apoptosis, as shown by increased TUNEL-positive cells in infarcted areas
• in response to chronic hypoxia (10% oxygen, 7 weeks), 4 of 6 homozygotes exhibit evidence of right ventricular infarcts which are less than 2 weeks old
• however, no left ventricular infarcts or coronary occlusion are observed

homeostasis/metabolism
• in response to chronic hypoxia (10% oxygen, 7 weeks), 4 of 6 homozygotes exhibit evidence of right ventricular infarcts which are less than 2 weeks old
• however, no left ventricular infarcts or coronary occlusion are observed
• 4-fold in mice infected with Plasmodium chabaudi chabaudi
• in response to chronic hypoxia (10% oxygen, 7 weeks), all (4 of 4) homozygotes with right ventricular infarcts display large, organized mural thrombi
• in mice infected with Plasmidium berhei ANKA

cellular
• in response to chronic hypoxia (10% oxygen, 7 weeks), homozygotes display increased cardiomyocyte apoptosis, as shown by increased TUNEL-positive cells in infarcted areas
• in response to chronic hypoxia (10% oxygen, 7 weeks), homozygotes show extensive lipid peroxidation and oxidative damage in the zone of right ventricular infarctions

muscle
• in response to chronic hypoxia (10% oxygen, 7 weeks), homozygotes display increased cardiomyocyte apoptosis, as shown by increased TUNEL-positive cells in infarcted areas

immune system
• mice infected with Plasmodium chabaudi chabaudi (PCC) exhibit increased mortality and hepatic failure with a 4-fold increase in alanine aminotransferase plasma concentration and accumulation of thiobarbituric acid reactive substances compared with control mice
• mice infected with Plasmidium berhei ANKA exhibit increased cerebral malaria as indicated by brain edema compared with control mice
• however, mice infected with PCC exhibit normal parasitemia and do not develop cerebral malaria or kidney failure
• all mice infected with Plasmodium chabaudi chabaudi die unlike control mice without an increase in parasitemia

liver/biliary system
• in mice infected with Plasmodium chabaudi chabaudi

Mouse Models of Human Disease
OMIM IDRef(s)
Malaria, Susceptibility to 611162 J:153083