mortality/aging
|
• about 20% of mice die between 7 and 23 weeks of age
|
reproductive system
| N |
• in vitro, oocyte-cumulus cell complexes retrieved from eCG-primed ovaries of adult homozygotes display normal follicular growth and oocyte maturation
• in vitro-matured oocytes obtained from adult female homozygotes show no significant differences in fertilization or preimplantation development
|
|
|
• extrusion of the first polar body is rarely noted
|
|
|
• pseudopregnant female homozygotes fail to exhibit an increase in uterine weight in response to intraluminal infusion of oil (a deciduogenic stimulus)
• intraluminal infusion of PGI2 (but not PGE2) or cholera toxin as the deciduogenic stimulus partially restores decidualization in ovaroectomized steroid hormonally prepared mutant mice
|
|
|
• females homozygotes exhibit significantly reduced superovulation, despite normal ovarian response to gonadotropins
(J:43609)
• any recovered eggs appear developmentally abnormal, with virtually no extrusion of the first polar body
(J:43609)
• adult (2- to 8-month-old) female homozygotes exhibit a poor ovulation rate upon induction with eCG and hCG
(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
(J:69034)
|
|
|
• 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
• failure of implantation and subsequent decidualization occur despite normal uterine responsiveness to steroid hormones
|
|
|
• number of term pregnancies reduced
(J:109548)
• only 20% of homozygous females can sustain term pregnancy
(J:118171)
|
|
• homozygous females produce small litters compared to wild-type
|
|
• female homozygotes display complete failure of fertilization, despite the presence of numerous sperm at the fertilization site
|
embryo
|
|
• pseudopregnant female homozygotes fail to exhibit an increase in uterine weight in response to intraluminal infusion of oil (a deciduogenic stimulus)
• intraluminal infusion of PGI2 (but not PGE2) or cholera toxin as the deciduogenic stimulus partially restores decidualization in ovaroectomized steroid hormonally prepared mutant mice
|
renal/urinary system
| N |
• adult mice exhibit normal urinalysis and 24-hr urine output under non-stressed conditions
• no significant differences in urine osmolarity or in daily urinary excretion of sodium, potassium and chloride are observed
|
kidney cyst
(
J:104002
)
|
• 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
|
|
• by P14, all mice exhibit outer cortical dysplasia
• inner cortical nephron hypertrophy by P42
|
|
• small, crowded glomeruli in subcapsular region at P10
(J:104002)
• outer cortical glomerular hypoplasia at P42
(J:104002)
• hypoplastic
(J:109548)
• average glomerular diameter is reduced to 29.4 um from 39.2 um in wild-type
(J:118171)
|
|
• 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
|
|
• focally variable glomerular sclerosis by P42
(J:104002)
• however, no inflammatory infiltrate or vascular pathology is observed at any age
(J:104002)
• moderate
(J:109548)
|
|
• 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
|
small kidney
(
J:109548
)
|
• 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
|
|
• at 8 weeks of age, some mice exhibit more severe cystic degeneration than others
|
pale kidney
(
J:109548
)
|
• adult mice exhibit a ~50% reduction in GFR relative to wild-type controls, as measured by inulin clearance
|
|
• mice exhibit progressive renal insufficiency
|
cardiovascular system
| N |
• normal systolic blood pressure in awake or anesthetized mice relative to wild-type controls
|
|
• fails to close in 40% of mice
|
|
• 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
|
|
• dye extravasation in the ear vasculature is decreased by 50-60% with bradykinin challenge compared to wild-type
|
digestive/alimentary system
|
• at 5 months of age, mice show chronic peritonitis
|
homeostasis/metabolism
| N |
• adult mice exhibit normal plasma sodium, potassium, bicarbonate and chloride levels relative to wild-type controls
|
|
• 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
(J:104002)
• BUN levels are increased ~2-fold vs wild-type at 6 months of age
(J:118171)
|
|
• near absence of LPS induced synthesis
|
immune system
|
• at 5 months of age, mice show chronic peritonitis
|
behavior/neurological
| N |
• mice exhibit normal daily water intake under non-stressed conditions
|
growth/size/body
| N |
• mice display normal somatic growth from birth to 42 days of age
|
|
• 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
|
kidney cyst
(
J:104002
)
|
• 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
|
cellular
|
• fails to close in 40% of mice
|
|
|
• extrusion of the first polar body is rarely noted
|


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