Phenotypes associated with this allele

• Allele Symbol: Comt^tm1Kara
• Allele Name: targeted mutation 1, Maria Karayiorgou
• Allele ID: MGI:2178542
• Summary: 3 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Comt^tm1Kara/Comt^tm1Kara	B6.129S4-Comt^tm1Kara	MGI:4830779
hm2	Comt^tm1Kara/Comt^tm1Kara	involves: 129S4/SvJaeSor	MGI:3697681
ht3	Comt^tm1Kara/Comt^+	involves: 129S4/SvJaeSor	MGI:3697682

Genotype
MGI:4830779

hm1

• Allelic Composition: Comt^tm1Kara/Comt^tm1Kara
• Genetic Background: B6.129S4-Comt^tm1Kara

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

homeostasis/metabolism

increased dopamine level ( J:164057 )

• elevated levels of dopamine in both the striatum and the medial prefrontal cortex in females compared with the values in the corresponding wild-type mice after oral administration of L-DOPA

abnormal xenobiotic pharmacokinetics ( J:164057 )

• an increase in plasma and liver L-DOPA in both sexes and intestinal L-DOPA levels in males after oral administration of L-DOPA, compared to wild-type

Genotype
MGI:3697681

hm2

• Allelic Composition: Comt^tm1Kara/Comt^tm1Kara
• Genetic Background: involves: 129S4/SvJaeSor

behavior/neurological

increased anxiety-related response ( J:49475 )

• displayed by females in light/dark box tests

• anxiety indicators in males are normal

cardiovascular system

abnormal placenta vasculature ( J:137276 )

• 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

hypertension ( J:137276 )

• 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

abnormal placenta morphology ( J:137276 )

• 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

abnormal placenta vasculature ( J:137276 )

• 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

abnormal maternal decidual layer morphology ( J:137276 )

♀ • arteriopathy in mutants resembles decidual vascular lesions (acute atherosis) in women with pre-eclampsia

increased uterine NK cell number ( J:137276 )

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

abnormal spongiotrophoblast layer morphology ( J:137276 )

• Nos3 expression in the spongiotrophoblast layer of the placenta is decreased in pregnant mutants compared to pregnant controls

hematopoietic system

increased uterine NK cell number ( J:137276 )

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

homeostasis/metabolism

abnormal homeostasis ( J:137276 )

• pregnant females exhibit only minimal levels of 2-methoxyestradiol (2-ME), a metabolite of oestradiol

abnormal blood homeostasis ( J:137276 )

• plasma sFLT-1 is higher in pregnant mutants than in pregnant controls starting at day 14 of pregnancy

increased dopamine level ( J:49475 )

• 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

hypoxia ( J:137276 )

• 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

albuminuria ( J:137276 )

• 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

increased uterine NK cell number ( J:137276 )

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

increased interferon-gamma secretion ( J:137276 )

• levels of decidual IFN-gamma are higher in pregnant mutants than pregnant wild-type females

renal/urinary system

albuminuria ( J:137276 )

• urinary albumin excretion is higher on day 17 of pregnancy in mutant females than wild-type females

• administration of 2-ME prevents the proteinuria

abnormal renal glomerulus morphology ( J:137276 )

• 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

abnormal maternal decidual layer morphology ( J:137276 )

♀ • arteriopathy in mutants resembles decidual vascular lesions (acute atherosis) in women with pre-eclampsia

increased uterine NK cell number ( J:137276 )

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

short gestation period ( J:137276 )

♀ • females deliver preterm: 19 days after confirmation of a vaginal plug compared to 20.4 days in wild-type mice

abnormal pregnancy ( J:137276 )

♀ • 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

abnormal fertility/fecundity ( J:137276 )

• females have a higher total number of embryos that wild-type

endocrine/exocrine glands

increased uterine NK cell number ( J:137276 )

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

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
cognitive disorder		DOID:1561		J:49475
pre-eclampsia		DOID:10591	OMIM:189800 OMIM:609402 OMIM:609403 OMIM:609404 OMIM:614592	J:137276

Genotype
MGI:3697682

ht3

• Allelic Composition: Comt^tm1Kara/Comt⁺
• Genetic Background: involves: 129S4/SvJaeSor

behavior/neurological

increased aggression towards male mice ( J:49475 )

• heterozygous males show increased aggression toward other males as compared to either homozygous or wild-type males