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
• 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
• 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/body
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
• in DSS-treated mice 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

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
• 8 days after wounding, endothelial cell staining at the site of the wound is increased 70% compared to in similarly treated wild-type mice
• the tensile strength of skin at the site of wound healing is 70% less than 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)

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
• at 8 weeks, homozygotes with peritonitis exhibit multiple fibrinous adhesions among the abdominal organs
• 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
• at 8 weeks, homozygotes with peritonitis exhibit multiple fibrinous adhesions among the abdominal organs

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
• 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
• 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/body
• 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

cellular


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

cellular
• 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

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

cellular
• 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