Phenotypes Associated with This Genotype

Genotype
MGI:2177807

• Allelic Composition: Ptgs1^tm1Unc/Ptgs1^tm1Unc
• Genetic Background: involves: 129P2/OlaHsd * C57BL/6

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

mortality/aging

increased susceptibility to xenobiotic induced morbidity/mortality ( J:60668 )

• in a model of acute DSS-induced colitis, homozygotes display increased mortality in response to 10% DSS, with only a 50% survival rate on day 5; in contrast, all wild-type mice survive the 5-day treatment

perinatal lethality, incomplete penetrance ( J:64073 )

• birthing is delayed resulting in decreased survival of pups

• however, treatment with PGF2alpha or PGE2 increase pup survival

growth/size/body

enlarged spleen ( J:60668 )

• in DSS-treated mice compared with similarly treated wild-type mice

reproductive system

abnormal corpus luteum morphology ( J:50148 )

♀ • at day 19 of gestation, mutant corpora lutea retain obvious vascular spaces, a uniform cellular morphology, and an organized luteal architecture, indicating delayed luteolysis

abnormal parturition ( J:50148 )

♀ • the delivery of homozygous mutant litters is significantly retarded (21.6 0.2 days) relative to the delivery of wild-type litters (19.6 0.2 days); once initiated, labor progresses rapidly

♀ • many of the pups arising from matings of homozygous deficient parents die perinatally despite normal pup size, degree of development, and litter size

♀ • likewise, matings of homozygous mutant females with wild-type or heterozygous males result in delayed delivery at day 22 0.5 of gestation with reduced fetal viability

♀ • administration of prostaglandin F receptor to homozygous mutant matings at day 19.5 of gestation results in labor within 24 hrs and restores neonatal viability

♀ • matings of homozygous mutant males with heterozygous females do not result in increased neonatal mortality, suggesting that female heterozygotes exhibit a normal onset of labor

delayed parturition ( J:64073 )

• birthing is delayed resulting in decreased survival of pups

• Background Sensitivity: delayed in birthing are greater than on a CD-1 mixed background

• however, parturition length is normal and treatment with PGF2alpha or PGE2 decreased delayed birthing

abnormal uterine environment ( J:29511 )

♀ • both male and female homozygotes are fertile and survive well; however, pup survival is severely reduced when homozygous mutant mice are mated to each other, despite normal litter sizes

homeostasis/metabolism

abnormal response of heart to induced stress ( J:103388 )

• following ischemia, recovery of contractile function is lower than in similarly treated wild-type mice

• however, pre-conditioned mice exhibit normal recovery from myocardial ischemia

increased circulating progesterone level ( J:50148 )

• at day 19 of gestation, gravid female homozygotes exhibit significantly higher plasma progesterone concentrations relative to wild-type mice

• in addition, induction of uterine oxytocin receptors is delayed

abnormal blood coagulation ( J:29511 )

decreased platelet aggregation ( J:29511 )

• in vitro, platelets from homozygous mutant mice aggregate more slowly and to a lesser extent than wild-type platelets in response to arachidonic acid

decreased prostaglandin level ( J:29511 , J:50148 , J:60668 , J:103388 , J:117986 )

• homozygous mutant peritoneal macrophages display a >99% reduction in basal PGE2 production relative to wild-type macrophages (J:29511)

• at day 19 of gestation, female homozygotes have uterine PGF2alpha concentrations only 1-3% of those found in wild-type or Oxt^tm1Ljm mutant females; ovarian concentrations are also severely reduced (J:50148)

• homozygotes exhibit loss of constitutive mucosal PGE2 production in unstimulated tissues, including the colon, stomach, duodenum, jejunum, ileum, and cecum; their colonic PGE2 concentrations are equal to those of wild-type controls after DSS-induced injury (J:60668)

• pre- and post-ischemia compared with similarly treated wild-type mice (J:103388)

• in keratinocyte cultures (J:117986)

abnormal urine homeostasis ( J:110043 )

• during sleep, mice exhibit higher normetanephrine (52%) and reduced prostaglandin (76%) and nitrate plus nitrite (35%) excretion compared with wild-type mice

• mice exhibit less of a reduction in normetanephrine excretion during sleep compared with wild-type mice

• however, awake time excretion of prostaglandin, nitrate plus nitrite, aldosterone, sodium, and potassium is normal

decreased urine prostaglandin level ( J:110043 )

• during sleep, mice exhibit reduced prostaglandin (76%) excretion compared with wild-type mice

• however, awake time excretion of prostaglandin is normal

increased susceptibility to xenobiotic induced morbidity/mortality ( J:60668 )

• in a model of acute DSS-induced colitis, homozygotes display increased mortality in response to 10% DSS, with only a 50% survival rate on day 5; in contrast, all wild-type mice survive the 5-day treatment

decreased physiological sensitivity to xenobiotic ( J:146321 )

• mice do not exhibit a decrease in internal anal sphincter muscle tone when treated with SC-560 unlike similarly treated wild-type mice

• however, mice exhibit normal sensitivity to the Ptsg2 inhibitor rofecoxib

increased susceptibility to injury ( J:60668 )

• in a model of acute dextran sodium sulfate (DSS)-induced colitis, homozygotes display increased susceptibility to a low-dose (2.5%) of DSS that causes mild colonic epithelial injury in wild-type mice

• notably, homozygotes treated with low-dose DSS display intermediate damage of the colonic mucosa relative to wild-type and Ptgs2^tm1Unc homozygous mutant mice

immune system

increased susceptibility to induced colitis ( J:60668 , J:158426 )

• in response to low-dose (2.5%) DSS-induced colitis, homozygotes display a significantly higher clinical score than wild-type mice (days 4 and 5), based on diarrhea, fecal blood, and weight loss (J:60668)

• DSS-treated homozygotes display intermediate values of colonic shortening, crypt damage, splenomegaly, leukocytosis and anemia relative to DSS-treated wild-type and Ptgs2^tm1Unc mutant mice (J:60668)

• pharmacological treatment with a selective PTGS2 inhibitor worsens low-dose DSS-induced colitis and enhances mortality (J:60668)

• mice treated with azoxymethane and dextran sulfate sodium exhibit greater weight loss compared with similarly treated wild-type mice (J:158426)

enlarged spleen ( J:60668 )

• in DSS-treated mice compared with similarly treated wild-type mice

increased susceptibility to endotoxin shock ( J:75611 )

• LPS-treated mice exhibit more weight loss than similarly treated wild-type mice

decreased inflammatory response ( J:29511 )

• F2 homozygotes show a significantly reduced inflammatory response (~30% of wild-type) to topical application of arachidonic acid, as determined by ear thickness

• in contrast, homozygotes exhibit a normal inflammatory response to tumor promoter TPA

cardiovascular system

abnormal blood flow velocity ( J:110043 )

• under anesthesia, renal blood flow is reduced compared to in similarly treated wild-type mice

increased renal vascular resistance ( J:110043 )

• under anesthesia

abnormal circadian regulation of systemic arterial blood pressure ( J:110043 )

• the ratio of sleep to wake blood pressure is 8.6% higher than in wild-type mice

abnormal circadian regulation of heart rate ( J:110043 )

• the ratio of sleep to wake heart rate is 5.7% higher than in wild-type mice

abnormal response of heart to induced stress ( J:103388 )

• following ischemia, recovery of contractile function is lower than in similarly treated wild-type mice

• however, pre-conditioned mice exhibit normal recovery from myocardial ischemia

increased mean systemic arterial blood pressure ( J:110043 )

• during sleep or under anesthesia

renal/urinary system

increased renal vascular resistance ( J:110043 )

• under anesthesia

abnormal urine homeostasis ( J:110043 )

• during sleep, mice exhibit higher normetanephrine (52%) and reduced prostaglandin (76%) and nitrate plus nitrite (35%) excretion compared with wild-type mice

• mice exhibit less of a reduction in normetanephrine excretion during sleep compared with wild-type mice

• however, awake time excretion of prostaglandin, nitrate plus nitrite, aldosterone, sodium, and potassium is normal

decreased urine prostaglandin level ( J:110043 )

• during sleep, mice exhibit reduced prostaglandin (76%) excretion compared with wild-type mice

• however, awake time excretion of prostaglandin is normal

abnormal kidney morphology ( J:29511 )

• at 2-5 months, 3 of 6 kidneys examined display one or two small foci per section of basophilic, immature tubules; the size and frequency of these lesions does not change with age

• all other tissues (including liver, spleen, GI and reproductive tract, lung and heart) appear microscopically normal

increased renal glomerular filtration rate ( J:110043 )

• under anesthesia

endocrine/exocrine glands

abnormal corpus luteum morphology ( J:50148 )

♀ • at day 19 of gestation, mutant corpora lutea retain obvious vascular spaces, a uniform cellular morphology, and an organized luteal architecture, indicating delayed luteolysis

digestive/alimentary system

digestive/alimentary phenotype ( J:29511 , J:60668 )

N • F2 and F3 homozygotes are generally healthy and do not develop spontaneous gastric ulcers but display reduced gastric ulceration after gavage with indomethacin relative to wild-type mice (J:29511)

N • homozygotes do not exhibit any clinical or histologic signs of spontaneous gastrointestinal inflammation, despite significantly reduced mucosal PGE2 levels (J:60668)

increased susceptibility to induced colitis ( J:60668 , J:158426 )

• in response to low-dose (2.5%) DSS-induced colitis, homozygotes display a significantly higher clinical score than wild-type mice (days 4 and 5), based on diarrhea, fecal blood, and weight loss (J:60668)

• DSS-treated homozygotes display intermediate values of colonic shortening, crypt damage, splenomegaly, leukocytosis and anemia relative to DSS-treated wild-type and Ptgs2^tm1Unc mutant mice (J:60668)

• pharmacological treatment with a selective PTGS2 inhibitor worsens low-dose DSS-induced colitis and enhances mortality (J:60668)

• mice treated with azoxymethane and dextran sulfate sodium exhibit greater weight loss compared with similarly treated wild-type mice (J:158426)

hematopoietic system

enlarged spleen ( J:60668 )

• in DSS-treated mice compared with similarly treated wild-type mice

decreased platelet aggregation ( J:29511 )

• in vitro, platelets from homozygous mutant mice aggregate more slowly and to a lesser extent than wild-type platelets in response to arachidonic acid

muscle

hypotonia ( J:146321 )

• in the internal anal sphincter

neoplasm

neoplasm ( J:158426 )

N • mice treated with azoxymethane and dextran sulfate sodium exhibit wild-type colon tumor incidence and histology

integument

abnormal keratinocyte differentiation ( J:117986 )

• keratinocyte cultures exhibit a 5-fold increase in expression of K1, a marker of differentiation, compared with wild-type cells

cellular

abnormal keratinocyte differentiation ( J:117986 )

• keratinocyte cultures exhibit a 5-fold increase in expression of K1, a marker of differentiation, compared with wild-type cells