Phenotypes associated with this allele

• Allele Symbol: Hmox1^tm1Mlee
• Allele Name: targeted mutation 1, Mu-En Lee
• Allele ID: MGI:2429784
• Summary: 2 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Hmox1^tm1Mlee/Hmox1^tm1Mlee	B6.129S2-Hmox1^tm1Mlee	MGI:3625884
hm2	Hmox1^tm1Mlee/Hmox1^tm1Mlee	involves: 129S2/SvPas * BALB/c	MGI:2429786

Genotype
MGI:3625884

hm1

• Allelic Composition: Hmox1^tm1Mlee/Hmox1^tm1Mlee
• Genetic Background: B6.129S2-Hmox1^tm1Mlee

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

cardiovascular system

abnormal artery morphology ( J:106600 )

• in response to vascular injury in femoral arteries, homozygotes display hyperplastic arteries relative to wild-type mice (intima:media area ratios of arterial lesions, 2.0 +/- 0.3 versus 1.1 +/- 0.2, respectively)

abnormal vascular smooth muscle physiology ( J:106600 )

• mutant VSMCs exhibit enhanced DNA synthesis and growth relative to wild-type VSMCs, as a result of facilitated G1/S entry

increased vascular smooth muscle cell proliferation ( J:106600 )

• in response to vascular injury, homozygotes exhibit a ~5-fold increase in VSMC proliferation in femoral arteries relative to wild-type mice

cellular

increased vascular smooth muscle cell proliferation ( J:106600 )

• in response to vascular injury, homozygotes exhibit a ~5-fold increase in VSMC proliferation in femoral arteries relative to wild-type mice

muscle

abnormal vascular smooth muscle physiology ( J:106600 )

• mutant VSMCs exhibit enhanced DNA synthesis and growth relative to wild-type VSMCs, as a result of facilitated G1/S entry

increased vascular smooth muscle cell proliferation ( J:106600 )

• in response to vascular injury, homozygotes exhibit a ~5-fold increase in VSMC proliferation in femoral arteries relative to wild-type mice

Genotype
MGI:2429786

hm2

• Allelic Composition: Hmox1^tm1Mlee/Hmox1^tm1Mlee
• Genetic Background: involves: 129S2/SvPas * BALB/c

mortality/aging

increased susceptibility to parasitic infection induced morbidity/mortality ( J:153083 )

• all mice infected with Plasmodium chabaudi chabaudi die unlike control mice without an increase in parasitemia

perinatal lethality, incomplete penetrance ( J:54684 )

• only ~20% of newborn homozygotes are obtained from heterozygote breedings, suggesting partial perinatal lethality

postnatal lethality, incomplete penetrance ( J:54684 )

• at 3 weeks, only about 7% of homozygotes are obtained from heterozygote matings; surviving homozygotes appear grossly normal

cardiovascular system

myocardium necrosis ( J:54684 )

• 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

increased heart right ventricle weight ( J:54684 )

• in response to chronic hypoxia (10% oxygen, 7 weeks), homozygotes exhibit a greater increase in right ventricular weight relative to wild-type mice

dilated heart right ventricle ( J:54684 )

• 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

cardiac fibrosis ( J:54684 )

• 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

abnormal response to cardiac infarction ( J:54684 )

• 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

abnormal response to cardiac infarction ( J:54684 )

• 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

increased circulating alanine transaminase level ( J:153083 )

• 4-fold in mice infected with Plasmodium chabaudi chabaudi

abnormal thrombosis ( J:54684 )

• in response to chronic hypoxia (10% oxygen, 7 weeks), all (4 of 4) homozygotes with right ventricular infarcts display large, organized mural thrombi

cerebral edema ( J:153083 )

• in mice infected with Plasmidium berhei ANKA

cellular

increased cardiomyocyte apoptosis ( J:54684 )

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

oxidative stress ( J:54684 )

• 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

myocardium necrosis ( J:54684 )

• 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

increased cardiomyocyte apoptosis ( J:54684 )

• 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

increased susceptibility to parasitic infection ( J:153083 )

• 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

increased susceptibility to parasitic infection induced morbidity/mortality ( J:153083 )

• all mice infected with Plasmodium chabaudi chabaudi die unlike control mice without an increase in parasitemia

liver/biliary system

liver failure ( J:153083 )

• in mice infected with Plasmodium chabaudi chabaudi

nervous system

cerebral edema ( J:153083 )

• in mice infected with Plasmidium berhei ANKA

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
malaria		DOID:12365		J:153083