Phenotypes Associated with This Genotype

Genotype
MGI:2175008

• Allelic Composition: Ptgir^tm1Sna/Ptgir^tm1Sna
• Genetic Background: involves: 129P2/OlaHsd * C57BL/6

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

mortality/aging

mortality/aging ( J:42275 )

N • homozygotes that survive to birth grow normally, are fertile and live >1 year in the absence of overt abnormalities

prenatal lethality, incomplete penetrance ( J:42275 )

• breeding of heterozygotes produces homozygotes at a lower frequency than the predicted Mendelian ratio, suggesting embryonic loss esp. in males

homeostasis/metabolism

abnormal blood coagulation ( J:42275 )

• homozygotes fail to exhibit prolonged bleeding times in response to beraprost (a prostacyclin mimetic), unlike wild-type mice

abnormal platelet activation ( J:79049 )

• in response to catheter-induced carotid vascular injury, homozygotes display enhanced platelet activation, as shown by an increased injury-related increment in urinary excretion of metabolite 2,3-dinor-TxB₂

increased susceptibility to induced thrombosis ( J:42275 , J:108957 )

• homozygotes do not develop spontaneous thrombosis but exhibit increased susceptibility to arterial thrombosis induced by FeCl₃ (J:42275)

• at 4 hrs after FeCl₃ exposure, ~2/3 of mutant arteries exhibit obstructive thrombi with reddish tails, whereas wild-type preparations display mural thrombi of yellowish color (J:42275)

• after prolonged FeCl₃ treatment, 30% of homozygotes die within 1 day due to bilateral occlusions of the carotid arteries and/or embolic stroke, whereas all wild-type mice survive treatment (J:42275)

• carotid artery occlusion time after photochemical injury is shortened (J:108957)

decreased prostaglandin level ( J:42275 )

• homozygotes show a normal prostacyclin concentration in the peritoneal lavage fluid after dilute acetic acid treatment; in contrast, PGE2 levels are reduced to ~25% of prostacyclin levels

abnormal thromboxane level ( J:79049 )

• after catheter-induced carotid vascular injury, homozygotes show an increased periprocedural increment in urinary metabolite 2,3-dinor-TxB₂

immune system

decreased acute inflammation ( J:42275 )

• in the carrageenin-induced paw-edema model, homozygotes exhibit reduced edema formation similar to that observed in indomethacin-pretreated wild-type mice

• in addition, homozygotes display a marked reduction of exudate volume in the carrageenin-induced pleurisy model

behavior/neurological

increased chemical nociceptive threshold ( J:42275 )

• in the acetic acid-induced writhing test, homozygotes exhibit reduced nociceptive perception to levels noted in indomethacin-pretreated wild-type mice

• notably, prostacyclin induces a writhing response in 60% of wild-type mice and in 0% of mutant mice, whereas PGE2 induces a response in less than 25% of animals in both genotypes

cardiovascular system

cardiovascular system phenotype ( J:42275 )

N • under basal conditions, homozygotes are normotensive and exhibit a normal heart rate and normal bleeding times relative to wild-type mice

vascular restenosis ( J:79049 )

• in response to catheter-induced carotid vascular injury, homozygotes exhibit an increased % of luminal stenosis relative to wild-type mice

abnormal cardiovascular system physiology ( J:79049 )

abnormal blood vessel physiology ( J:79049 )

• in response to catheter-induced carotid vascular injury, homozygotes exhibit enhanced vascular proliferative indices, as shown by a significant increase in the intima-to-media ratio, % of luminal stenosis, and the number of intimal and medial BrdU-labeled cells relative to wild-type mice

hematopoietic system

abnormal platelet activation ( J:79049 )

• in response to catheter-induced carotid vascular injury, homozygotes display enhanced platelet activation, as shown by an increased injury-related increment in urinary excretion of metabolite 2,3-dinor-TxB₂