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Phenotypes Associated with This Genotype
Genotype
MGI:3697681
Allelic
Composition
Comttm1Kara/Comttm1Kara
Genetic
Background
involves: 129S4/SvJaeSor
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Comttm1Kara mutation (0 available); any Comt mutation (23 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
behavior/neurological
• displayed by females in light/dark box tests
• anxiety indicators in males are normal

cardiovascular system
• arteries in the decidua of mutant pregnant females contain hyaline-like deposits with foam cells in the wall and thrombosis in the lumen
• these vascular lesions have non-specific IgM deposition in the vessel walls
• vascular defects are not observed in any other organ of pregnant mutant females
• level of von Willebrand factor is diminished in the thrombotic vascular lesions, suggesting endothelial damage
• administration of 2-ME diminishes the vascular abnormalities
• mutant females exhibit a fluctuation of blood pressure on day 10 of pregnancy that increases significantly compared to wild-type pregnant females or non-pregnant mutant females, indicating gestational hypertension
• blood pressure returns to normal levels within 10 days after delivery
• administration of 2-ME prevents the increase in blood pressure

embryo
• placentae/decidua on day 17 of pregnancy weigh less than those of wild-type mice
• administration of 2-ME restores weight of placentae/decidua to normal levels
• abundant eosin-positive deposition is seen in the placentae/decidua of mutant females
• arteries in the decidua of mutant pregnant females contain hyaline-like deposits with foam cells in the wall and thrombosis in the lumen
• these vascular lesions have non-specific IgM deposition in the vessel walls
• vascular defects are not observed in any other organ of pregnant mutant females
• level of von Willebrand factor is diminished in the thrombotic vascular lesions, suggesting endothelial damage
• administration of 2-ME diminishes the vascular abnormalities
• arteriopathy in mutants resembles decidual vascular lesions (acute atherosis) in women with pre-eclampsia
• numbers of decidual NK cells are higher in pregnant mutants than pregnant wild-type females
• Nos3 expression in the spongiotrophoblast layer of the placenta is decreased in pregnant mutants compared to pregnant controls

hematopoietic system
• numbers of decidual NK cells are higher in pregnant mutants than pregnant wild-type females

homeostasis/metabolism
• pregnant females exhibit only minimal levels of 2-methoxyestradiol (2-ME), a metabolite of oestradiol
• plasma sFLT-1 is higher in pregnant mutants than in pregnant controls starting at day 14 of pregnancy
• 2-3X increased levels in the frontal cortex of males only
• levels are normal in the hypothalamus and striatum although the homovanillic acid/dihydroxyphenylacetic acid ratios are significantly altered
• on day 17 of pregnancy, placenta and decidua show signs of hypoxia in mutant females
• hypoxia is seen predominantly in the spongiotrophoblast layer of the placenta
• urinary albumin excretion is higher on day 17 of pregnancy in mutant females than wild-type females
• administration of 2-ME prevents the proteinuria

immune system
• numbers of decidual NK cells are higher in pregnant mutants than pregnant wild-type females
• levels of decidual IFN-gamma are higher in pregnant mutants than pregnant wild-type females

renal/urinary system
• urinary albumin excretion is higher on day 17 of pregnancy in mutant females than wild-type females
• administration of 2-ME prevents the proteinuria
• mutant females exhibit kidney glomerular endothelial cell detachment, swelling and vacuolization (endotheliosis) on day 17 of pregnancy
• pregnant females treated with 2-ME do not exhibit glomerular lesions

reproductive system
• arteriopathy in mutants resembles decidual vascular lesions (acute atherosis) in women with pre-eclampsia
• numbers of decidual NK cells are higher in pregnant mutants than pregnant wild-type females
• females deliver preterm: 19 days after confirmation of a vaginal plug compared to 20.4 days in wild-type mice
• pregnant mutant females show a higher fetal wastage at E17 compared to wild-type
• administration of 2-ME to females decreases fetal wastage, however administration of oestradiol or 2-hydroxyoestradiol does not
• females have a higher total number of embryos that wild-type

endocrine/exocrine glands
• numbers of decidual NK cells are higher in pregnant mutants than pregnant wild-type females


Contributing Projects:
Mouse Genome Database (MGD), Gene Expression Database (GXD), Mouse Models of Human Cancer database (MMHCdb) (formerly Mouse Tumor Biology (MTB)), Gene Ontology (GO)
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last database update
03/12/2024
MGI 6.23
The Jackson Laboratory