cardiovascular system phenotype

• cardiac fibrosis
  • 50% of adult homozygotes exhibit diffuse myocardial fibrosis of variable severity involving both right and left ventricles
  (MGI Ref ID J:29974)

renal/urinary system phenotype

• abnormal kidney corticomedullary boundary morphology
  • homozygous newborns exhibit corticomedullary atrophy
  (MGI Ref ID J:29974)

• abnormal renal glomerulus morphology
  • all adult homozygotes exhibit mild to moderate renal lesions typified by numerous immature small glomeruli found subcapsularly
  (MGI Ref ID J:29974)

• abnormal kidney collecting duct morphology
  • homozygous newborns show poor collecting duct development
  (MGI Ref ID J:29974)

• abnormal renal tubule morphology
  • all adult homozygotes exhibit mild to moderate renal lesions typified by multiple foci of dysplastic tubules
  (MGI Ref ID J:29974)

• abnormal kidney development
  • although fetal metanephri appear normal at E14, kidneys of homozygous newborns appear severely underdeveloped relative to wild-type kidneys
  (MGI Ref ID J:29974)

• abnormal kidney mesenchyme morphology
  • homozygous newborns show abundant undifferentiated mesenchyme
  (MGI Ref ID J:29974)

• kidney corticomedullary cysts
  • all adult homozygotes display corticomedullary microcysts
  (MGI Ref ID J:29974)

• kidney medulla hypoplasia
  • all adult homozygotes display mild medullary hypoplasia or atrophy
  (MGI Ref ID J:29974)

• pyelonephritis
  • all adult homozygotes with renal histopathology are susceptible to development of secondary pyelonephritis
  (MGI Ref ID J:29974)

• abnormal kidney cortex morphology
  (MGI Ref ID J:29974)

• abnormal kidney morphology
  • all adult homozygotes exhibit renal dysplasia
  (MGI Ref ID J:29974)

• kidney failure
  • adult homozygotes die of chronic renal failure of developmental origin
  (MGI Ref ID J:29974)

endocrine/exocrine gland phenotype

• absent corpus luteum
  • mutant ovaries show virtual absence of corpora lutea, despite normal ovarian follicular development
  (MGI Ref ID J:29974)

• small ovary
  (MGI Ref ID J:29974)

reproductive system phenotype

• absent corpus luteum
  • mutant ovaries show virtual absence of corpora lutea, despite normal ovarian follicular development
  (MGI Ref ID J:29974)

• female infertility
  • homozygous females are largely infertile, rarely giving birth to live offspring
  (MGI Ref ID J:29974)

• decreased ovulation rate
  (MGI Ref ID J:29974)

• small ovary
  (MGI Ref ID J:29974)

homeostasis/metabolism phenotype

• increased circulating creatinine level
  (MGI Ref ID J:29974)

• increased blood urea nitrogen level
  (MGI Ref ID J:29974)

immune system phenotype

• pyelonephritis
  • all adult homozygotes with renal histopathology are susceptible to development of secondary pyelonephritis
  (MGI Ref ID J:29974)

mammalian phenotype

• hematopoietic system phenotype
  • Normal - homozygotes exhibit normal hematologic parameters
  (MGI Ref ID J:29974)

• immune system phenotype
  • Normal - homozygotes exhibit normal immune responses to carrageenan-induced paw edema, TPA-induced edema and arachidonic acid-induced edema
  (MGI Ref ID J:29974)

mortality/aging

• neonatal lethality, incomplete penetrance
  • ~65% of homozygous mutant mice die neonatally
  (MGI Ref ID J:29974)

• premature death
  • homozygotes that reach weaning have an average lifespan of ~3.5 months, with a few animals surviving beyond 6 months
  (MGI Ref ID J:29974)

immune system phenotype

• abnormal response to infection
  • Normal - improved clearance is not the result of increased macrophage or neutrophil recruitment or cytokine production as these measures are similar to wild-type controls
  (MGI Ref ID J:120725)
  • following infection with Pseudomonas aeruginosa (PA103) bacterila counts in the right lung are lower compared to wild-type controls
  (MGI Ref ID J:120725)

cardiovascular system phenotype

• decreased vascular permeability
  • dye extravasation in the ear vasculature is decreased by 50-60% with bradykinin challenge compared to wild-type
  (MGI Ref ID J:118171)

• increased heart weight
  • Normal - however, a normal ratio is observed during postnatal growth and early adulthood
  (MGI Ref ID J:104002)
  • at birth, mice exhibit a significantly higher heart weight:body weight ratio relative to control mice
  (MGI Ref ID J:104002)

• patent ductus arteriosus
  • fails to close in 40% of mice
  (MGI Ref ID J:109548)

growth/size/body region phenotype

• increased heart weight
  • at birth, mice exhibit a significantly higher heart weight:body weight ratio relative to control mice
  (MGI Ref ID J:104002)
  • Normal - however, a normal ratio is observed during postnatal growth and early adulthood
  (MGI Ref ID J:104002)

homeostasis/metabolism phenotype

• decreased prostaglandin level
  • near absence of LPS induced synthesis
  (MGI Ref ID J:109548)

• increased circulating creatinine level
  • adult mice exhibit a 1.5-fold increase in plasma creatinine levels relative to controls
  (MGI Ref ID J:104002)

• increased blood urea nitrogen level
  • adult mice exhibit a 2.5-fold increase in plasma BUN levels relative to controls
  (MGI Ref ID J:104002)
  • BUN levels are increased ~2-fold vs wild-type at 6 months of age
  (MGI Ref ID J:118171)

immune system phenotype

• peritoneal inflammation
  • at 5 months of age, mice show chronic peritonitis
  (MGI Ref ID J:118171)

mammalian phenotype

• behavior/neurological phenotype
  • Normal - mice exhibit normal daily water intake under non-stressed conditions
  (MGI Ref ID J:104002)

• reproductive system phenotype
  • Normal - in vitro, oocyte-cumulus cell complexes retrieved from eCG-primed ovaries of adult homozygotes display normal follicular growth and oocyte maturation
  (MGI Ref ID J:69034)
  • Normal - in vitro-matured oocytes obtained from adult female homozygotes show no significant differences in fertilization or preimplantation development
  (MGI Ref ID J:69034)
  • also, in vitro-matured oocytes obtained from adult female homozygotes show no significant differences in fertilization or preimplantation development
  (MGI Ref ID J:69034)
  • in vitro, oocyte-cumulus cell complexes retrieved from eCG-primed ovaries of adult homozygotes display normal follicular growth and oocyte maturation
  (MGI Ref ID J:69034)

• growth/size/body region phenotype
  • Normal - mice display normal somatic growth from birth to 42 days of age
  (MGI Ref ID J:104002)

• cardiovascular system phenotype
  • Normal - normal systolic blood pressure in awake or anesthetized mice relative to wild-type controls
  (MGI Ref ID J:104002)

• renal/urinary system phenotype
  • Normal - no significant differences in urine osmolarity or in daily urinary excretion of sodium, potassium and chloride are observed
  (MGI Ref ID J:104002)
  • Normal - adult mice exhibit normal urinalysis and 24-hr urine output under non-stressed conditions
  (MGI Ref ID J:104002)

• homeostasis/metabolism phenotype
  • Normal - adult mice exhibit normal plasma sodium, potassium, bicarbonate and chloride levels relative to wild-type controls
  (MGI Ref ID J:104002)

mortality/aging

• premature death
  • about 20% of mice die between 7 and 23 weeks of age
  (MGI Ref ID J:104002)

renal/urinary system phenotype

• abnormal renal glomerulus morphology
  • average glomerular diameter is reduced to 29.4 um from 39.2 um in wild-type
  (MGI Ref ID J:118171)
  • outer cortical glomerular hypoplasia at P42
  (MGI Ref ID J:104002)
  • small, crowded glomeruli in subcapsular region at P10
  (MGI Ref ID J:104002)
  • hypoplastic
  (MGI Ref ID J:109548)

• decreased kidney weight
  • starting at P10, total kidney mass is significantly reduced relative to that in wild-type controls
  (MGI Ref ID J:104002)
  • kidney-specific growth suppression persists to P42 with no significant change
  (MGI Ref ID J:104002)

• glomerulosclerosis
  • Normal - however, no inflammatory infiltrate or vascular pathology is observed at any age
  (MGI Ref ID J:104002)
  • moderate
  (MGI Ref ID J:109548)
  • focally variable glomerular sclerosis by P42
  (MGI Ref ID J:104002)

• kidney failure
  • mice exhibit progressive renal insufficiency
  (MGI Ref ID J:104002)

• renal glomerulus fibrosis
  • peri-glomerular fibrosis by P42
  (MGI Ref ID J:104002)

• renal glomerulus hypertrophy
  • hypertrophy of juxtamedullary glomeruli at P28
  (MGI Ref ID J:104002)
  • inner cortical glomerular hypertrophy by P42
  (MGI Ref ID J:104002)

• kidney degeneration
  • at 8 weeks of age, some mice exhibit more severe cystic degeneration than others
  (MGI Ref ID J:104002)

• dilated renal tubules
  • variable tubular dilation at P10
  (MGI Ref ID J:104002)
  • severe diffuse tubular dilation by P42
  (MGI Ref ID J:104002)

• kidney cortex atrophy
  (MGI Ref ID J:109548)

• kidney cortex cysts
  • massive tubular cysts in severely affected kidneys at P14
  (MGI Ref ID J:104002)

• renal glomerulus cysts
  • by P14, all mice exhibit cystic subcapsular glomeruli
  (MGI Ref ID J:104002)

• abnormal kidney cortex morphology
  • by P14, all mice exhibit outer cortical dysplasia
  (MGI Ref ID J:104002)
  • inner cortical nephron hypertrophy by P42
  (MGI Ref ID J:104002)

• decreased renal glomerular filtration rate
  • adult mice exhibit a ~50% reduction in GFR relative to wild-type controls, as measured by inulin clearance
  (MGI Ref ID J:104002)

• kidney cysts
  • early cystic changes affecting different tubule sections and glomeruli at P10, with slightly variable pathologic progression
  (MGI Ref ID J:104002)
  • severe cyst formation by P28
  (MGI Ref ID J:104002)

• proximal convoluted tubule brush border loss
  • by P14, all mice exhibit loss of brush border definition
  (MGI Ref ID J:104002)

• pale kidney
  (MGI Ref ID J:109548)

• renal interstitial fibrosis
  • diffuse interstitial fibrosis by P42
  (MGI Ref ID J:104002)

• small kidney
  (MGI Ref ID J:109548)

• abnormal proximal convoluted tubule morphology
  • variable loss of normal proximal tubule mantle at P10
  (MGI Ref ID J:104002)

• cortical renal glomerulopathies
  • at >6 weeks of age, renal cortex is abnormal with small immature glomeruli and deteriorating tubules; these changes are not seen in 2-month old COX-1 knockin mice
  (MGI Ref ID J:118171)

• renal tubule hypertrophy
  • hypertrophy of juxtamedullary tubules by P28
  (MGI Ref ID J:104002)

• abnormal kidney development
  • Normal - however, prenatal and early postnatal kidney development appears normal
  (MGI Ref ID J:104002)
  • mice exhibit progressive cystic dysplasia during the later stages of kidney development
  (MGI Ref ID J:104002)

• renal tubule atrophy
  • by P14, all mice exhibit loss of proximal tubular mass
  (MGI Ref ID J:104002)

cellular phenotype

• abnormal primary polar body morphology
  • extrusion of the first polar body is rarely noted
  (MGI Ref ID J:43609)

• patent ductus arteriosus
  • fails to close in 40% of mice
  (MGI Ref ID J:109548)

reproductive system phenotype

• abnormal primary polar body morphology
  • extrusion of the first polar body is rarely noted
  (MGI Ref ID J:43609)

• abnormal superovulation
  • any recovered eggs appear developmentally abnormal, with virtually no extrusion of the first polar body
  (MGI Ref ID J:43609)
  • adult (2- to 8-month-old) female homozygotes exhibit a poor ovulation rate upon induction with eCG and hCG
  (MGI Ref ID J:69034)
  • immature (3-week-old) female homozygotes exhibit a superior ovulation rate relative to adult homozygotes, suggesting that the ovulatory process becomes defective with aging
  (MGI Ref ID J:69034)
  • females homozygotes exhibit significantly reduced ovulation, despite normal ovarian response to gonadotropins
  (MGI Ref ID J:43609)

• decreased litter size
  • homozygous females produce small litters compared to wild-type
  (MGI Ref ID J:118171)

• impaired fertilization
  • female homozygotes display complete failure of fertilization, despite the presence of numerous sperm at the fertilization site
  (MGI Ref ID J:43609)

• reduced female fertility
  • only 20% of homozygous females can sustain term pregnancy
  (MGI Ref ID J:118171)
  • number of term pregnancies reduced
  (MGI Ref ID J:109548)

• abnormal decidualization
  • pseudopregnant female homozygotes fail to exhibit an increase in uterine weight in response to intraluminal infusion of oil (a deciduogenic stimulus)
  (MGI Ref ID J:43609)
  • intraluminal infusion of PGI2 (but not PGE2) or cholera toxin as the deciduogenic stimulus partially restores decidualization in ovaroectomized steroid hormonally prepared mutant mice
  (MGI Ref ID J:43609)

• failure of embryo implantation
  • failure of implantation and subsequent decidualization occur despite normal uterine responsiveness to steroid hormones
  (MGI Ref ID J:43609)
  • in blastocyst transfer experiments, wild-type blastocysts fail to exhibit the initial attachment reaction and do not implant into uteri of pseudopregnant female homozygous mutant mice
  (MGI Ref ID J:43609)

digestive/alimentary phenotype

• peritoneal inflammation
  • at 5 months of age, mice show chronic peritonitis
  (MGI Ref ID J:118171)

embryo phenotype

• abnormal decidualization
  • pseudopregnant female homozygotes fail to exhibit an increase in uterine weight in response to intraluminal infusion of oil (a deciduogenic stimulus)
  (MGI Ref ID J:43609)
  • intraluminal infusion of PGI2 (but not PGE2) or cholera toxin as the deciduogenic stimulus partially restores decidualization in ovaroectomized steroid hormonally prepared mutant mice
  (MGI Ref ID J:43609)

digestive/alimentary phenotype

• abnormal stomach pH
  • indomethacin-treated mice exhibit a less prominent disruption in pH gradient in the stomach compared with similarly treated wild-type mice
  (MGI Ref ID J:103642)

homeostasis/metabolism phenotype

• decreased physiological sensitivity to xenobiotic
  • indomethacin-treated mice exhibit a less prominent disruption in pH gradient in the stomach compared with similarly treated wild-type mice
  (MGI Ref ID J:103642)

respiratory system phenotype

• pulmonary interstitial fibrosis
  • in response to bleomycin-induced lung injury, homozygotes exhibit an aggressive fibroproliferative response, widespread inflammation, loss of alveolar architecture, and increased extracellular matrix protein deposition relative to wild-type mice
  (MGI Ref ID J:68669)