Analysis Tools
growth/size/body
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• homozygotes with peritonitis exhibit myeloid hyperplasia in their spleen
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mortality/aging
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• mice that survive the postnatal period survive weaning
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• several mice die at ~8 weeks of age
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• 35% of mice die within the first 24 to 48 hrs of birth
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• 35% of mice die within the first 24 to 48 hrs of birth
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reproductive system
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• 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
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• 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)
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• 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
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• at 8 hrs after hCG treatment, PMSG-primed homozygotes exhibit lack of organized cumulus granulosa cell polarization or expansion
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• at 24-30 hrs after hCG treatment, only 2 of nine PMSG-primed homozygotes ovulate, with only 2 or 3 isolated oocytes without cumulus mass
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• at 24-30 hrs after hCG treatment, 7 of nine PMSG-primed homozygotes exhibit absence of oocytes and cumulus mass in their oviducts
• ovulation is restored upon gonadotropin stimulation and simultaneous treatment with PGE2 or interleukin-1beta; treatment with PGF2alpha is less effective
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• female homozygotes exhibit estrous cyclicity and normal copulation but fail to impregnate and deliver viable pups, even after PMSG/hCG stimulation
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renal/urinary system
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• nephropathy is often associated with tubular dilation and interstitial inflammation
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• 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
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• by 8 weeks, mutant kidneys appear granular on the capsular surface
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• at 16 weeks, a single male survivor displays focal segmental and global glomerulosclerosis
• however, renal arteries and arterioles appear normal
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• at 6 weeks, abnormally low numbers of glomeruli are observed in the renal cortex
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• subcapsular glomerular hypoplasia occurs in conjunction with hypertrophy of deeper cortical glomeruli
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• homozygotes exhibit a postnatal maturation arrest in the subcapsular nephrogenic zone
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• homozygotes exhibit a postnatal maturation arrest in the subcapsular nephrogenic zone
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• 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
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• nephropathy is often associated with papillary mineralization
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small kidney
(
J:29510
)
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• at 8 weeks, mutant kidneys are small
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• in some cases, the kidney cortex appears thinned
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• 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
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• in mild cases, nephron hypoplasia in the subcapsular region is characterized by small immature glomeruli and tubules
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• nephropathy is often associated with tubular dilation
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renal cast
(
J:29510
)
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• nephropathy is often associated with protein and cellular casts in the tubular lumens
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• nephropathy is often associated with papillary mineralization
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• at 8 weeks, mutant kidneys are pale
(J:29510)
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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
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• at 8 weeks, homozygotes with peritonitis exhibit submucosal edema of the bowel wall
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• 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
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• 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)
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• hypoxia-treated mice exhibit increased fibrin and platelet depositions in retinal vessels compared to in similarly treated wild-type retinas
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• LPS-treated mice fail to exhibit an increase in core body temperature unlike similarly treated wild-type mice
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• 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
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• 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)
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cardiovascular system
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• following hypoxia-treatment, the area of retinal nonperfusion is increased compared to in similarly treated wild-type retinas
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• 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
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• basal blood pressure is greater than in wild-type mice
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• 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
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• 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
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immune system
| N |
• homozygotes display normal inflammatory responses to treatments with TPA or arachidonic acid, as measured by ear thickness
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• 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
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• homozygotes with peritonitis exhibit myeloid hyperplasia in their spleen
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• in culture, homozygous mutant peritoneal macrophages fail to exhibit LPS induction of PGE2 synthesis
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• homozygous females with peritonitis show significant lymphoplasmacytic hyperplasia of the mesenteric lymph node
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• nephropathy is often associated with tubular dilation and interstitial inflammation
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digestive/alimentary system
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• 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
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• at 8 weeks, homozygotes with peritonitis exhibit submucosal edema of the bowel wall
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• 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
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endocrine/exocrine glands
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• at 8 hrs after hCG treatment, PMSG-primed homozygotes exhibit lack of organized cumulus granulosa cell polarization or expansion
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• 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
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• 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)
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hematopoietic system
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• homozygotes with peritonitis exhibit myeloid hyperplasia in their spleen
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• in culture, homozygous mutant peritoneal macrophages fail to exhibit LPS induction of PGE2 synthesis
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liver/biliary system
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• 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
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vision/eye
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• following hypoxia-treatment, the area of retinal nonperfusion is increased compared to in similarly treated wild-type retinas
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cellular
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• 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
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• at 8 hrs after hCG treatment, PMSG-primed homozygotes exhibit lack of organized cumulus granulosa cell polarization or expansion
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