Mouse Genome Informatics
hm1
    Ptgs2tm1Unc/Ptgs2tm1Unc
B6.129P2-Ptgs2tm1Unc
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
immune system
• 21 days post-vaccination with HPV, mice exhibit 34% fewer B220+IgG1+ and 50% fewer B220+Ig2a+ cells compared to in wild-type mice
• however, IgG2b and IgG3 class switching is normal
• mice vaccinated with HPV-like particles exhibit reduced spleen memory B cell expansion compared with similarly treated wild-type mice
• 69% in mice vaccinated with HPV-like particles
• 89% in mice vaccinated with HPV-like particles
• 43% in mice vaccinated with HPV-like particles
• 4-fold in mice vaccinated with HPV-like particles
• FCA-treated female mice exhibit reduced joint destruction compared with similarly treated male wild-type mice
• mice vaccinated with HPV-like particles produce 70% fewer viral-like particle antibodies and 80% fewer viral-like particle antibody-secreting cells compared with similarly treated wild-type mice
• mice vaccinated with HPV-like particles produce more IgM and fewer IgG1 (69%), IgG2a (89%), and IgG3 (43%) antibodies compared to in similarly treated wild-type mice
• mice vaccinated with HPV-like particles produce more IgM producing cells and fewer IgG1 (78%), IgG2a (70%), IgG2b (15%), and IgG3 (55%) secreting cells compared with similarly treated wild-type mice
• mice vaccinated with HPV-like particles produce 10-fold fewer virus like particle-specific neutralizing antibodies compared to in similarly treated wild-type mice
• mice vaccinated with HPV-like particles exhibit reduced spleen memory B cell expansion compared with similarly treated wild-type mice

homeostasis/metabolism
• mice exhibit reduced NMDA-induced damage compared to in wild-type mice
• following occlusion of the middle cerebral artery, mice fail to exhibit an increase in cortical prostaglandin unlike similarly treated wild-type mice
• after 90 to 120 minutes, IL1beta-fed mice exhibit a reduced decrease in drinking behavior compared with similarly treated wild-type mice
• however, IL1beta-fed mice exhibit a normal decrease in drinking behavior after 30 minutes
• following occlusion of the middle cerebral artery, mice fail to exhibit an increase in cortical prostaglandin unlike similarly treated wild-type mice
• 96 hours after occlusion of the middle cerebral artery, infarct size is reduced 34% compared to in similarly treated wild-type mice
• 96 hours after occlusion of the middle cerebral artery, infarct size is reduced 38% compared to in similarly treated wild-type mice

nervous system
• mice exhibit reduced NMDA-induced damage compared to in wild-type mice
• following occlusion of the middle cerebral artery, mice fail to exhibit an increase in cortical prostaglandin unlike similarly treated wild-type mice
• 96 hours after occlusion of the middle cerebral artery, infarct size is reduced 34% compared to in similarly treated wild-type mice
• 96 hours after occlusion of the middle cerebral artery, infarct size is reduced 38% compared to in similarly treated wild-type mice

behavior/neurological
• after 90 to 120 minutes, IL1beta-fed mice exhibit a reduced decrease in drinking behavior compared with similarly treated wild-type mice
• however, IL1beta-fed mice exhibit a normal decrease in drinking behavior after 30 minutes
• FCA-treated mice fail to develop ipsilateral and contralateral mechanical allodynia unlike similarly treated wild-type mice
• FCA-treated mice fail to develop thermal hyperalgesia unlike similarly treated wild-type mice
• FCA-treated mice fail to develop ipsilateral and contralateral mechanical allodynia unlike similarly treated wild-type mice
• FCA-treated mice fail to develop thermal hyperalgesia unlike similarly treated wild-type mice

skeleton
• FCA-treated female mice exhibit reduced joint destruction compared with similarly treated male wild-type mice

hematopoietic system
• 21 days post-vaccination with HPV, mice exhibit 34% fewer B220+IgG1+ and 50% fewer B220+Ig2a+ cells compared to in wild-type mice
• however, IgG2b and IgG3 class switching is normal
• mice vaccinated with HPV-like particles exhibit reduced spleen memory B cell expansion compared with similarly treated wild-type mice
• 69% in mice vaccinated with HPV-like particles
• 89% in mice vaccinated with HPV-like particles
• 43% in mice vaccinated with HPV-like particles
• 4-fold in mice vaccinated with HPV-like particles

integument
• FCA-treated mice fail to develop ipsilateral and contralateral mechanical allodynia unlike similarly treated wild-type mice
• FCA-treated mice fail to develop thermal hyperalgesia unlike similarly treated wild-type mice
• FCA-treated mice fail to develop ipsilateral and contralateral mechanical allodynia unlike similarly treated wild-type mice
• FCA-treated mice fail to develop thermal hyperalgesia unlike similarly treated wild-type mice

cellular
• mice exhibit reduced NMDA-induced damage compared to in wild-type mice


Mouse Genome Informatics
hm2
    Ptgs2tm1Unc/Ptgs2tm1Unc
B6;129P2-Ptgs2tm1Unc/Tac
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
mortality/aging
• 3 of 18 kainate-treated mice die unlike similarly treated wild-type mice
• kainate-treated mice pretreated with the CB1 antagonist, AM-251, exhibit increased mortality compared with similarly treated wild-type mice

nervous system
• kainate-treated mice exhibit increased Racine seizure score, neuronal damage, and mortality compared with similarly treated wild-type mice
• pretreatment with the CB1 antagonist, AM-251, increases seizure intensity, neuronal damage, and mortality in kainate-treated mice unlike in similarly treated wild-type mice
• 5 of 18 kainate-treated mice reach maximal seizure intensity that includes tonic-clonic seizures unlike in similarly treated wild-type mice
• kainate-treated mice exhibit increased Racine seizure score, neuronal damage, and mortality compared with similarly treated wild-type mice
• the frequency of spontaneous inhibitory postsynaptic current is decreased 61% compared to in wild-type mice

homeostasis/metabolism
• kainate-treated mice exhibit increased Racine seizure score, neuronal damage, and mortality compared with similarly treated wild-type mice
• 3 of 18 kainate-treated mice die unlike similarly treated wild-type mice
• kainate-treated mice pretreated with the CB1 antagonist, AM-251, exhibit increased mortality compared with similarly treated wild-type mice
• following muscle injury, mice exhibit reduced inflammation compared with similarly treated wild-type mice
• healing bone fractures exhibit little or no callus with reduced bone formation and decreased endochondral ossification compared to in wild-type mice

skeleton
• healing bone fractures exhibit little or no callus with reduced bone formation and decreased endochondral ossification compared to in wild-type mice
• bone fractures exhibit little to no endochondral bone ossification unlike in similarly treated wild-type mice

muscle
• following muscle injury, mice exhibit reduced muscle regeneration and 31% smaller regenerating myofibers compared with wild-type mice

behavior/neurological
• kainate-treated mice exhibit increased Racine seizure score, neuronal damage, and mortality compared with similarly treated wild-type mice
• pretreatment with the CB1 antagonist, AM-251, increases seizure intensity, neuronal damage, and mortality in kainate-treated mice unlike in similarly treated wild-type mice
• 5 of 18 kainate-treated mice reach maximal seizure intensity that includes tonic-clonic seizures unlike in similarly treated wild-type mice

cellular
• kainate-treated mice exhibit increased Racine seizure score, neuronal damage, and mortality compared with similarly treated wild-type mice


Mouse Genome Informatics
hm3
    Ptgs2tm1Unc/Ptgs2tm1Unc
D1.129P2(B6J)-Ptgs2tm1Unc
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
mortality/aging
N
• Background Sensitivity: adult homozygotes do not exhibit reduced longevity, unlike homozygotes generated on a predominantly C57BL/6J background (J:64383)
• only 66% of homozygotes survive to weaning versus 92% of wild-type controls; however, no adult mice are found to die spontaneously during a 6-month study period
• Background Sensitivity: adult homozygotes do not die from renal failure, unlike homozygotes generated on a predominantly C57BL/6 background

renal/urinary system
• Background Sensitivity: adult homozygotes do not exhibit the severe renal pathology observed in homozygotes of a predominantly C57BL/6J genetic background
• hypoplastic subcapsular glomeruli are observed by P14 and become cystic as mice age, unlike in wild-type controls
• inner cortical hyperplastic glomeruli are seen at 3 weeks of age, unlike in wild-type controls
• undifferentiated mesenchyme is seen as early as P7, unlike in wild-type controls
• interstitial fibrosis is noted at 3 weeks and becomes prominent by 8 months of age
• mutant kidneys are smaller than wild-type
• at 34 weeks of age, the ratio of kidney weight to total body weight is significantly lower than that of wild-type controls
• mutant kidneys have a more granular surface than wild-type
• by 9 months of age, small subcapsular glomeruli are detected in cystic spaces
• Background Sensitivity: cystic changes are less severe than those observed on a predominantly C57BL/6 background
• mutant kidneys appear paler than wild-type

reproductive system
• female homozygous mutant mice are infertile (J:64383)

homeostasis/metabolism
• at 10, 16, 20 and 28 weeks of age, average plasma creatinine levels are significantly higher than in wild-type controls
• at 2-8 months of age, homozygotes show a ~2-fold increase in BUN levels relative to wild-type controls
• Background Sensitivity: increase in BUN levels is significantly lower than that reported for homozygotes on a B6 genetic background (200% versus 270%)

hematopoietic system
• hematocrit values are significantly lower than those of wild type controls at most time points during a 6-month study period

behavior/neurological
N
• both male and female homozygotes display normal reaction times in the hot plate test, indicating normal thermal nociception (J:64383)
• homozygotes appear to be less excitable and easier to handle than wild-type littermates
• docile behavior is most evident in female homozygotes


Mouse Genome Informatics
hm4
    Ptgs2tm1Unc/Ptgs2tm1Unc
D1.129P2-Ptgs2tm1Unc
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
homeostasis/metabolism
• fat pad tissue from mice fed a high fat and sucrose diet exhibit a 20% decrease in prostaglandin production compared with tissues from similarly treated wild-type mice


Mouse Genome Informatics
hm5
    Ptgs2tm1Unc/Ptgs2tm1Unc
involves: 129/Sv * 129P2/OlaHsd * C57BL/6
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
skeleton
• cultured bone marrow treated with 1,25-dihydroxyvitamin D3 (1,25-D) produce 96% less TRAP+ mononuclear cells (osteoclast) than similarly treated wild-type bone marrow
• parathyroid hormone (PTH)-stimulated bone marrow cultures produce fewer TRAP+ mononuclear cells (osteoclast) than similarly treated wild-type cultures
• 1,25-D-stimulated bone marrow cultures exhibit a 60% reduction in pit formation compared with similarly treated wild-type cultures
• spleen cells cultured with RANKL and M-CSF produce 2- to 3-fold fewer osteoclasts than similarly treated wild-type cells
• 1,25-D- or PTH-treated osteoblasts cocultured with wild-type or Ptgs2tm1Unc homozygous spleen cells exhibit reduced TRAP+ mononuclear cells (osteoclast) formation compared with similarly treated wild-type cells
• however, treatment of cultures with prostaglandin improves osteoclast formation

homeostasis/metabolism
• serum calcium levels in parathyroid hormone (PTH)-injected mice are lower than in similarly treated wild-type mice
• 1,25-dihydroxyvitamin D3 (1,25-D)-stimulated bone marrow cultures produce 99% lower prostaglandin levels compared with similarly treated wild-type cultures
• parathyroid hormone (PTH)-stimulated bone marrow cultures produce lower prostaglandin levels compared with similarly treated wild-type cultures

immune system
• cultured bone marrow treated with 1,25-dihydroxyvitamin D3 (1,25-D) produce 96% less TRAP+ mononuclear cells (osteoclast) than similarly treated wild-type bone marrow
• parathyroid hormone (PTH)-stimulated bone marrow cultures produce fewer TRAP+ mononuclear cells (osteoclast) than similarly treated wild-type cultures
• 1,25-D-stimulated bone marrow cultures exhibit a 60% reduction in pit formation compared with similarly treated wild-type cultures
• spleen cells cultured with RANKL and M-CSF produce 2- to 3-fold fewer osteoclasts than similarly treated wild-type cells
• 1,25-D- or PTH-treated osteoblasts cocultured with wild-type or Ptgs2tm1Unc homozygous spleen cells exhibit reduced TRAP+ mononuclear cells (osteoclast) formation compared with similarly treated wild-type cells
• however, treatment of cultures with prostaglandin improves osteoclast formation

hematopoietic system
• 1,25-D-stimulated bone marrow cultures exhibit a 60% reduction in pit formation compared with similarly treated wild-type cultures
• cultured bone marrow treated with 1,25-dihydroxyvitamin D3 (1,25-D) produce 96% less TRAP+ mononuclear cells (osteoclast) than similarly treated wild-type bone marrow
• parathyroid hormone (PTH)-stimulated bone marrow cultures produce fewer TRAP+ mononuclear cells (osteoclast) than similarly treated wild-type cultures
• spleen cells cultured with RANKL and M-CSF produce 2- to 3-fold fewer osteoclasts than similarly treated wild-type cells
• 1,25-D- or PTH-treated osteoblasts cocultured with wild-type or Ptgs2tm1Unc homozygous spleen cells exhibit reduced TRAP+ mononuclear cells (osteoclast) formation compared with similarly treated wild-type cells
• however, treatment of cultures with prostaglandin improves osteoclast formation
• serum calcium levels in parathyroid hormone (PTH)-injected mice are lower than in similarly treated wild-type mice

cellular
• cultured bone marrow treated with 1,25-dihydroxyvitamin D3 (1,25-D) produce 96% less TRAP+ mononuclear cells (osteoclast) than similarly treated wild-type bone marrow
• parathyroid hormone (PTH)-stimulated bone marrow cultures produce fewer TRAP+ mononuclear cells (osteoclast) than similarly treated wild-type cultures
• 1,25-D-stimulated bone marrow cultures exhibit a 60% reduction in pit formation compared with similarly treated wild-type cultures
• spleen cells cultured with RANKL and M-CSF produce 2- to 3-fold fewer osteoclasts than similarly treated wild-type cells
• 1,25-D- or PTH-treated osteoblasts cocultured with wild-type or Ptgs2tm1Unc homozygous spleen cells exhibit reduced TRAP+ mononuclear cells (osteoclast) formation compared with similarly treated wild-type cells
• however, treatment of cultures with prostaglandin improves osteoclast formation


Mouse Genome Informatics
hm6
    Ptgs2tm1Unc/Ptgs2tm1Unc
involves: 129P2/OlaHsd
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
digestive/alimentary system
N
• mice exhibit normal radiation-induced crypt epithelial cell apoptosis (J:108679)


Mouse Genome Informatics
hm7
    Ptgs2tm1Unc/Ptgs2tm1Unc
involves: 129P2/OlaHsd * C57BL/6
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
mortality/aging
• following treatment with a high dose of DSS, survival is decreased by day 4 and drops to 50% by day 5 whereas similarly treated wild-type mice do not exhibit any decrease in survival (J:60668)
• mice treated with azoxymethane and dextran sulfate sodium exhibit increased mortality compared with similarly treated wild-type mice (J:158426)
• about 20% of mice die between 7 and 23 weeks of age

immune system
• mice treated with a high dose of DSS exhibit increased weight loss, intestinal inflammation score, and mortality compared with similarly treated wild-type mice (J:60668)
• DSS-treated mice fail to exhibit an increase in colonic secretion of prostaglandin unlike similarly treated wild-type mice (J:60668)
• mice treated with a low dose of DSS exhibit increased clinical inflammation and weight lose compared with similarly treated wild-type mice (J:60668)
• DSS-treated mice exhibit increased colonic shortening, colonic weight to length ratio, splenomegaly, white blood cell counts, and crypt damage and decreased hematocrit compared with similarly treated wild-type mice (J:60668)
• DSS-treated mice exhibit a more aggressive mucosal injury than in similarly treated wild-type mice and Ptgs1tm1Unc homozygotes (J:60668)
• mice treated with azoxymethane and dextran sulfate sodium exhibit increased mortality compared with similarly treated wild-type mice (J:158426)
• in 2 of 10 mice unlike wild-type mice
• in DSS-treated mice compared with similarly treated wild-type mice
• in DSS-treated mice compared with similarly treated wild-type mice
• in the pancreas and bronchoalveolar lavage fluid of cerulein-treated mice compared with similarly treated wild-type mice
• LPS-treated mice exhibit less weight loss than similarly treated wild-type mice

digestive/alimentary system
• DSS-treated mice exhibit increased colonic shortening and colonic weight to length ratio compared with similarly treated wild-type mice
• mice treated with a high dose of DSS exhibit increased weight loss, intestinal inflammation score, and mortality compared with similarly treated wild-type mice (J:60668)
• DSS-treated mice fail to exhibit an increase in colonic secretion of prostaglandin unlike similarly treated wild-type mice (J:60668)
• mice treated with a low dose of DSS exhibit increased clinical inflammation and weight lose compared with similarly treated wild-type mice (J:60668)
• DSS-treated mice exhibit increased colonic shortening, colonic weight to length ratio, splenomegaly, white blood cell counts, and crypt damage and decreased hematocrit compared with similarly treated wild-type mice (J:60668)
• DSS-treated mice exhibit a more aggressive mucosal injury than in similarly treated wild-type mice and Ptgs1tm1Unc homozygotes (J:60668)
• mice treated with azoxymethane and dextran sulfate sodium exhibit increased mortality compared with similarly treated wild-type mice (J:158426)
• in 2 of 10 mice unlike wild-type mice

growth/size
N
• mice display normal somatic growth from birth to 42 days of age (J:104002)
• compared with wild-type mice when treated with a high or low dose of DSS

homeostasis/metabolism
N
• adult mice exhibit normal plasma sodium, potassium, bicarbonate and chloride levels relative to wild-type controls (J:104002)
• following ischemia, maximum contracture is higher and recovery of contractile function is lower than in similarly treated wild-type mice
• however, pre-conditioned mice exhibit normal recovery from myocardial ischemia
• adult mice exhibit a 1.5-fold increase in plasma creatinine levels relative to controls
• adult mice exhibit a 2.5-fold increase in plasma BUN levels relative to controls
• cerulein-treated mice exhibit reduced pancreatic and lung myeloperoxidase levels compared with similarly treated wild-type mice
• in the bronchoalvealor lavage fluid of cerulein-treated mice compared with similarly treated wild-type mice
• DSS-treated mice fail to exhibit an increase in colonic secretion of prostaglandin unlike similarly treated wild-type mice (J:60668)
• in keratinocyte cultures (J:117986)
• following treatment with a high dose of DSS, survival is decreased by day 4 and drops to 50% by day 5 whereas similarly treated wild-type mice do not exhibit any decrease in survival (J:60668)
• mice treated with azoxymethane and dextran sulfate sodium exhibit increased mortality compared with similarly treated wild-type mice (J:158426)
• mice treated with azoxymethane alone fail to develop colon tumors unlike similarly treated wild-type mice
• cerulein-treated mice exhibit less pancreatitis-associated lung injury compared with similarly treated wild-type mice

hematopoietic system
• DSS-treated mice exhibit reduced hematocrit compared with similarly treated wild-type mice
• DSS-treated mice exhibit reduced hematocrit compared with similarly treated wild-type mice
• in DSS-treated mice compared with similarly treated wild-type mice
• in DSS-treated mice compared with similarly treated wild-type mice

cardiovascular system
N
• normal systolic blood pressure in awake or anesthetized mice relative to wild-type controls (J:104002)
• at birth, mice exhibit a significantly higher heart weight:body weight ratio relative to control mice
• however, a normal ratio is observed during postnatal growth and early adulthood
• following ischemia, maximum contracture is higher and recovery of contractile function is lower than in similarly treated wild-type mice
• however, pre-conditioned mice exhibit normal recovery from myocardial ischemia

muscle
N
• mice exhibit normal internal anal sphincter muscle tone (J:146321)

endocrine/exocrine glands
• in cerulein-treated mice compared with similarly treated wild-type mice
• following supramaximally stimulating doses of cerulein, mice develop decreased pancreatitis and associated lung injury with reduced , acinar cell necrosis, pancreatic and lung myeloperoxidase activity, bronchoalveolar lavage (BAL) fluid lactate dehydrogenase levels, and pancreatic and BAL TNF-alpha levels compared with similarly treated wild-type mice

tumorigenesis
• mice treated with azoxymethane alone fail to develop colon tumors unlike similarly treated wild-type mice
• mice treated with azoxymethane and dextran sulfate sodium exhibit more colon tumors than similarly treated wild-type mice
• however, the histology of induced-tumors is the same as in similarly treated wild-type mice

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

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

renal/urinary system
N
• adult mice exhibit normal urinalysis and 24-hr urine output under non-stressed conditions (J:104002)
• no significant differences in urine osmolarity or in daily urinary excretion of sodium, potassium and chloride are observed (J:104002)
• by P14, all mice exhibit outer cortical dysplasia
• inner cortical nephron hypertrophy by P42
• small, crowded glomeruli in subcapsular region at P10
• outer cortical glomerular hypoplasia at P42
• focally variable glomerular sclerosis by P42
• however, no inflammatory infiltrate or vascular pathology is observed at any stage
• peri-glomerular fibrosis by P42
• hypertrophy of juxtamedullary glomeruli at P28
• inner cortical glomerular hypertrophy by P42
• mice exhibit progressive cystic dysplasia during the later stages of kidney development
• however, prenatal and early postnatal kidney development appears normal
• diffuse interstitial fibrosis by P42
• starting at P10, total kidney mass is significantly reduced relative to that in wild-type controls
• kidney-specific growth suppression persists to P42 with no significant change
• by P14, all mice exhibit loss of proximal tubular mass
• variable loss of normal proximal tubule mantle at P10
• by P14, all mice exhibit loss of brush border definition
• variable tubular dilation at P10
• severe diffuse tubular dilation by P42
• hypertrophy of juxtamedullary tubules by P28
• early cystic changes affecting different tubule sections and glomeruli at P10, with slightly variable pathologic progression
• severe cyst formation by P28
• massive tubular cysts in severely affected kidneys at P14
• by P14, all mice exhibit cystic subcapsular glomeruli
• at 8 weeks of age, some mice exhibit more severe cystic degeneration than others
• adult mice exhibit a ~50% reduction in GFR relative to wild-type controls, as measured by inulin clearance
• mice exhibit progressive renal insufficiency

behavior/neurological
N
• mice exhibit normal daily water intake under non-stressed conditions (J:104002)


Mouse Genome Informatics
hm8
    Ptgs2tm1Unc/Ptgs2tm1Unc
involves: 129P2/OlaHsd * C57BL/6 * DBA/1
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
homeostasis/metabolism
• the tensile strength of skin at the site of wound healing is 70% less than in similarly treated wild-type mice
• 8 days after wounding, endothelial cell staining at the site of the wound is increased 70% compared to in similarly treated wild-type mice


Mouse Genome Informatics
hm9
    Ptgs2tm1Unc/Ptgs2tm1Unc
involves: 129P2/OlaHsd * C57BL/6J
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
mortality/aging
• mice that survive the postnatal period survive weaning
• 35% of mice die within the first 24 to 48 hrs of birth
• 35% of mice die within the first 24 to 48 hrs of birth
• several mice die at ~8 weeks of age

reproductive system
• at 8 hrs after hCG treatment, PMSG-primed homozygotes exhibit lack of organized cumulus granulosa cell polarization or expansion (J:55145)
• at 24-36 hrs after hCG treatment, PMSG-primed mutant ovaries display formation of corpora hemorrhagica but oocytes remain in the antral cavity without exophytic, cellular ovulation sites around stigmata (J:55145)
• at 8 hrs after hCG treatment, PMSG-primed homozygotes exhibit attenuated or unorganized cumulus expansion, despite evidence of oocyte activation (i.e. germinal vesicle breakdown and resumption of meiosis) (J:55145)
• matings between F1 heterozygotes result in abnormal Mendelian ratios of male F2 progeny (28:20:12), whereas genotype ratios of female progeny are normal (15:31:11)
• however, equal numbers of males (60) and females (56) reach weaning age, despite differences in genotype ratios of male and female weanlings, suggesting a possible pre-implantation defect
• at 24-30 hrs after hCG treatment, 7 of nine PMSG-primed homozygotes exhibit absence of oocytes and cumulus mass in their oviducts; the remaining two ovulate, with only 2 or 3 isolated oocytes without cumulus mass (J:55145)
• notably, ovulation is restored upon gonadotropin stimulation and simultaneous treatment with PGE2 or interleukin-1beta; treatment with PGF2alpha is less effective (J:55145)
• female homozygotes exhibit estrous cyclicity and normal copulation but fail to impregnate and deliver viable pups, even after PMSG/hCG stimulation (J:55145)

renal/urinary system
• nephropathy is often associated with tubular dilation and interstitial inflammation
• abnormal renal pathology is first noted at ~6 weeks and progresses with increasing age; males are more severely affected than females
• all adult homozygotes show renal lesions of mild to marked severity
• however, normal renal histology, with a normal subcapsular (immature) nephrogenic zone and normal numbers of glomeruli are observed in the renal cortex at 3 weeks of age
• by 8 weeks, mutant kidneys appear granular on the capsular surface
• at 16 weeks, a single male survivor displays focal segmental and global glomerulosclerosis
• however, renal arteries and arterioles appear normal
• at 6 weeks, abnormally low numbers of glomeruli are observed in the renal cortex
• subcapsular glomerular hypoplasia occurs in conjunction with hypertrophy of deeper cortical glomeruli
• homozygotes exhibit a postnatal maturation arrest in the subcapsular nephrogenic zone
• homozygotes exhibit a postnatal maturation arrest in the subcapsular nephrogenic zone
• at 8 weeks, affected kidneys show a few small scattered foci of interstitial fibrosis, not seen at 6 weeks of age
• at 16 weeks, a single male survivor displays severe focal interstitial fibrosis
• nephropathy is often associated with papillary mineralization
• at 8 weeks, mutant kidneys are small
• in some cases, the kidney cortex appears thinned
• at 8 weeks, affected kidneys show a few small scattered foci of tubular atrophy, not seen at 6 weeks of age
• at 16 weeks, a single male survivor displays severe tubular atrophy
• in mild cases, nephron hypoplasia in the subcapsular region is characterized by small immature glomeruli and tubules
• nephropathy is often associated with tubular dilation
• nephropathy is often associated with protein and cellular casts in the tubular lumens
• nephropathy is often associated with papillary mineralization
• at 8 weeks, mutant kidneys are pale (J:29510)

homeostasis/metabolism
N
• PMSG-primed homozygotes display normal serum estradiol levels and normal serum progesterone levels at 8 and 24 hrs after hCG treatment, respectively (J:55145)
• at 8 weeks, homozygotes with peritonitis exhibit submucosal edema of the bowel wall
• homozygotes exhibit significantly increased pituitary FSH contents relative to wild-type mice
• in addition, homozygotes tend to exhibit higher serum FSH values relative to wild-type mice
• homozygotes tend to exhibit increased pituitary LH levels relative to wild-type mice
• in contrast, mutants show no significant changes in hypothalamic tissue levels of gonadotropin releasing hormone 1 (GNRH1; also, LHRH)
• hypoxia-treated mice exhibit increased fibrin and platelet depositions in retinal vessels compared to in similarly treated wild-type retinas
• LPS-treated mice fail to exhibit an increase in core body temperature unlike similarly treated wild-type mice
• brains contain 15% more phosphatidylserine and 37%, 27%, and 32% less triacylglycerol and cholesterol concentrations and cholesterol-to-phospholipid ratio, respectively, than in wild-type brains
• at 48 hrs after PMSG treatment, homozygotes show reduced PGE2 levels relative to wild-type mice (J:55145)
• at 8 hrs after hCG treatment, PMSG-primed wild-type ovaries exhibit a 4-fold increase in PGE2 contents, whereas PGE2 values remain unchanged in mutant ovaries (J:55145)
• in the retina (J:109021)
• at 8 weeks, homozygotes with peritonitis exhibit multiple fibrinous adhesions among the abdominal organs

cardiovascular system
• following hypoxia-treatment, the area of retinal nonperfusion is increased compared to in similarly treated wild-type retinas
• 33% of mice that die within the first 48 hrs of birth exhibit patent ductus arteriosus
• unlike in wild type mice, treatment with indomethacin does not induce premature closure of the ductus arteriosus and associated neonatal lethality
• basal blood pressure is greater than in wild-type mice
• during the inactive day and active night, mice exhibit increased diastolic blood pressure compared with wild-type mice
• however, stress induced changes in blood pressure are normal
• during the inactive day and active night, mice exhibit increased systolic blood pressure compared with wild-type mice
• however, stress induced changes in blood pressure are normal

immune system
N
• homozygotes display normal inflammatory responses to treatments with TPA or arachidonic acid, as measured by ear thickness (J:29510)
• 2 of 7 homozygotes examined at ~8 weeks exhibit suppurative peritonitis
• suppurative peritonitis is acute in male homozygotes and chronic in female homozygotes
• in affected males, peritonitis involves multiple abdominal organs and is typified by purulent exudate, focal acute inflammation of the muscularis, and focal accumulation of rod-like bacteria
• homozygotes with peritonitis exhibit myeloid hyperplasia in their spleen
• in culture, homozygous mutant peritoneal macrophages fail to exhibit LPS induction of PGE2 synthesis
• homozygous females with peritonitis show significant lymphoplasmacytic hyperplasia of the mesenteric lymph node
• nephropathy is often associated with tubular dilation and interstitial inflammation

digestive/alimentary system
• at 8 weeks, homozygotes with peritonitis exhibit submucosal edema of the bowel wall, associated with a prominent neutrophilic infiltrate and leukocytoclasia (necrosis)
• in affected females, abscesses and chronic inflammatory tissue between lobes of the liver and loops of the bowel are observed
• at 8 weeks, homozygotes with peritonitis exhibit submucosal edema of the bowel wall
• 2 of 7 homozygotes examined at ~8 weeks exhibit suppurative peritonitis
• suppurative peritonitis is acute in male homozygotes and chronic in female homozygotes
• in affected males, peritonitis involves multiple abdominal organs and is typified by purulent exudate, focal acute inflammation of the muscularis, and focal accumulation of rod-like bacteria

endocrine/exocrine glands
• at 8 hrs after hCG treatment, PMSG-primed homozygotes exhibit lack of organized cumulus granulosa cell polarization or expansion (J:55145)
• at 24-36 hrs after hCG treatment, PMSG-primed mutant ovaries display formation of corpora hemorrhagica but oocytes remain in the antral cavity without exophytic, cellular ovulation sites around stigmata (J:55145)
• at 8 hrs after hCG treatment, PMSG-primed homozygotes exhibit attenuated or unorganized cumulus expansion, despite evidence of oocyte activation (i.e. germinal vesicle breakdown and resumption of meiosis) (J:55145)

hematopoietic system
• homozygotes with peritonitis exhibit myeloid hyperplasia in their spleen
• in culture, homozygous mutant peritoneal macrophages fail to exhibit LPS induction of PGE2 synthesis

liver/biliary system
• mice that die within the first 48 hrs after birth exhibit macrovesicular and microvesicular lipid deposits in the liver consistent with acute ischemia secondary to heart failure

vision/eye
• following hypoxia-treatment, the area of retinal nonperfusion is increased compared to in similarly treated wild-type retinas

cellular
• at 8 hrs after hCG treatment, PMSG-primed homozygotes exhibit lack of organized cumulus granulosa cell polarization or expansion (J:55145)


Mouse Genome Informatics
ht10
    Ptgs2tm1Unc/Ptgs2+
B6.129P2-Ptgs2tm1Unc
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
homeostasis/metabolism
• following occlusion of the middle cerebral artery, mice exhibit an attenuated increase in cortical prostaglandin compared with similarly treated wild-type mice
• 96 hours after occlusion of the middle cerebral artery, infarct size is reduced 20% compared to in similarly treated wild-type mice

nervous system
• 96 hours after occlusion of the middle cerebral artery, infarct size is reduced 20% compared to in similarly treated wild-type mice


Mouse Genome Informatics
ht11
    Ptgs2tm1Unc/Ptgs2+
D1.129P2(B6J)-Ptgs2tm1Unc
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
behavior/neurological
• heterozygous female mutants exhibit fewer writhing responses and decreased nociception in the acetic acid-induced stretch model of algesia

integument
• heterozygous female mutants exhibit fewer writhing responses and decreased nociception in the acetic acid-induced stretch model of algesia


Mouse Genome Informatics
ht12
    Ptgs2tm1Unc/Ptgs2+
D1.129P2-Ptgs2tm1Unc
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
homeostasis/metabolism
• mice fed a high fat and sucrose diet exhibit a 24% greater increase in body weight compared with similarly treated wild-type mice and a 34% increase compared with homozygotes
• in mice fed a high fat and sucrose diet compared to in similarly treated wild-type mice or homozygotes
• leptin serum levels are 336% higher in mice fed a high fat and sucrose diet compared to in similarly treated wild-type mice
• fat pad tissue from mice fed a high fat and sucrose diet exhibit a 2-fold increase in prostaglandin production compared with tissues from similarly treated wild-type mice

adipose tissue
• mice fed a high fat and sucrose diet exhibit a 134% increase in fat pad weight compared to in similarly treated wild-type mice and 328% increase compared to in similarly treated homozygotes
• cultured adipose tissue from mice fed a high fat and sucrose diet exhibit increased leptin released compared with adipose tissue from similarly treated wild-type mice or homozygotes

growth/size
• at 7 to 8 weeks, mice fed breeder chow (10% fat) exhibit increased body weight compared with wild-type mice
• however, after 28 weeks mice exhibit normal body weights when fed breeder chow
• mice fed a high fat and sucrose diet exhibit a 24% greater increase in body weight compared with similarly treated wild-type mice and a 34% increase compared with homozygotes


Mouse Genome Informatics
ht13
    Ptgs2tm1Unc/Ptgs2+
involves: 129/Sv * 129P2/OlaHsd * C57BL/6
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
skeleton
• cultured bone marrow treated with 1,25-dihydroxyvitamin D3 (1,25-D) produce 50% less TRAP+ mononuclear cells (osteoclast) than similarly treated wild-type bone marrow

homeostasis/metabolism
• 1,25-dihydroxyvitamin D3 (1,25-D)-stimulated bone marrow cultures produce 62% lower prostaglandin levels compared with similarly treated wild-type cultures

immune system
• cultured bone marrow treated with 1,25-dihydroxyvitamin D3 (1,25-D) produce 50% less TRAP+ mononuclear cells (osteoclast) than similarly treated wild-type bone marrow

hematopoietic system
• cultured bone marrow treated with 1,25-dihydroxyvitamin D3 (1,25-D) produce 50% less TRAP+ mononuclear cells (osteoclast) than similarly treated wild-type bone marrow

cellular
• cultured bone marrow treated with 1,25-dihydroxyvitamin D3 (1,25-D) produce 50% less TRAP+ mononuclear cells (osteoclast) than similarly treated wild-type bone marrow


Mouse Genome Informatics
ht14
    Ptgs2tm1Unc/Ptgs2+
involves: 129P2/OlaHsd * C57BL/6J
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
homeostasis/metabolism
• LPS-treated mice fail to exhibit an increase in core body temperature unlike similarly treated wild-type mice

cardiovascular system
• during the inactive day and active night, mice exhibit increased systolic blood pressure compared with wild-type mice
• however, stress induced changes in blood pressure are normal


Mouse Genome Informatics
ht15
    Ptgs2tm1Unc/Ptgs2tm2.1Hahe
involves: 129P2/OlaHsd * 129S4/SvJae * C57BL/6
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
mortality/aging
• mice treated with azoxymethane and dextran sulfate sodium exhibit increased mortality compared with similarly treated wild-type mice

immune system
• mice treated with azoxymethane and dextran sulfate sodium exhibit increased mortality compared with similarly treated wild-type mice

tumorigenesis
N
• mice treated with azoxymethane and dextran sulfate sodium exhibit wild-type colon tumor incidence and histology (J:158426)

digestive/alimentary system
• mice treated with azoxymethane and dextran sulfate sodium exhibit increased mortality compared with similarly treated wild-type mice

homeostasis/metabolism
• mice treated with azoxymethane and dextran sulfate sodium exhibit increased mortality compared with similarly treated wild-type mice


Mouse Genome Informatics
cx16
    Ptgs1tm1Unc/Ptgs1tm1Unc
Ptgs2tm1Unc/Ptgs2tm1Unc

involves: 129P2/OlaHsd * C57BL/6 * CD-1
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
mortality/aging
• mice die within 24 hours of birth with wide patent ductus arterious

cardiovascular system


Mouse Genome Informatics
cx17
    Hrhr/Hrhr
Ptgs2tm1Unc/Ptgs2tm1Unc

involves: 129P2/OlaHsd * C57BL/6 * SKH1
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
mortality/aging
• mice do not survive beyond several weeks of age


Mouse Genome Informatics
cx18
    Hrhr/Hrhr
Ptgs2tm1Unc/Ptgs2+

involves: 129P2/OlaHsd * C57BL/6 * SKH1
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
tumorigenesis
• after 14 weeks of UV treatment, mice fail to develop tumors unlike similarly treated SKH mice and do not develop tumors until 24 weeks of treatment
• UV-treated mice exhibit a 65% reduction in tumor number and decreased tumor incidence compared with similarly treated wild-type mice

homeostasis/metabolism
• 50% in the epidermis

cellular
• skin from UV-treated mice exhibits 50% less basal cell proliferation than in skin from similarly treated wild-type mice


Mouse Genome Informatics
cx19
    Ptgs1tm1Unc/Ptgs1tm1Unc
Ptgs2tm1Unc/Ptgs2tm1Unc

involves: 129P2/OlaHsd * C57BL/6J
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
mortality/aging
• more than 50% of mice become cyanotic and die within the first 30 minutes of Caesarian delivery
• 100% of mice die within the first 48 hours of birth

cardiovascular system
• all mice exhibit patent ductus arteriosus
• unlike in wild type mice, treatment with indomethacin does not induce premature closure of the ductus arteriosus and associated neonatal lethality

respiratory system
• in mice that die within the first 30 minutes of delivery

homeostasis/metabolism
• more than 50% of mice become cyanotic and die within the first 30 minutes of Caesarian delivery

Mouse Models of Human Disease
OMIM IDRef(s)
Patent Ductus Arteriosus 607411 J:67208


Mouse Genome Informatics
cx20
    Ptgs1tm1Unc/Ptgs1+
Ptgs2tm1Unc/Ptgs2tm1Unc

involves: 129P2/OlaHsd * C57BL/6J
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
mortality/aging
• 79% of mice die within the first 48 hours of birth

cardiovascular system
• 74% of mice that die within the first 48 hrs of birth exhibit patent ductus arteriosus


Mouse Genome Informatics
cx21
    Ptgs1tm1Unc/Ptgs1+
Ptgs2tm1Unc/Ptgs2+

involves: 129P2/OlaHsd * C57BL/6J
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
reproductive system
• parturition is delayed (J:67208)


Mouse Genome Informatics
cx22
    Ptgs1tm1Unc/Ptgs1tm1Unc
Ptgs2tm1Unc/Ptgs2+

involves: 129P2/OlaHsd * C57BL/6J
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
reproductive system
• parturition is delayed (J:67208)


Mouse Genome Informatics
cx23
    ApcMin/Apc+
Ptgs2tm1Unc/Ptgs2tm1Unc

involves: 129P2/OlaHsd * C57BL/6J
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
mortality/aging
• mice survive 1 year unlike ApcMin heterozygotes that die after 7 to 8 months

tumorigenesis
• mice form 84% fewer, smaller intestinal tumors compared with ApcMin heterozygotes

homeostasis/metabolism
• intestinal tumor tissue fails to exhibit an increase in prostaglandin levels unlike in ApcMin heterozygotes

digestive/alimentary system