Analysis Tools
mortality/aging
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• 50% die within the first 4-5 months of life
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growth/size/body
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• progressive enlargement of the esophagus apparent at 8 days of age but not at birth
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weight loss
(
J:70078
)
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• weight is normal during the first week after birth
• weight gain is slower from the second week on
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behavior/neurological
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• eventually absent
|
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• normal at 1-2 months of age but diminishing thereafter and eventually disappears
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• widened stance
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abnormal gait
(
J:70078
)
|
• minimal alternation between right and left side
• frequently fail to fully lift each foot between steps
|
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• in older animals
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hearing/vestibular/ear
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• eventually the near complete loss of hair cells, first the outer hair cells and then the inner hair cells
|
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• enlarged blood vessels in the stria vascularis
• no identifiable blood vessels at 11 months of age
|
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• almost completely degenerated by 11 months of age
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• elevated auditory thresholds are observed; in one case, the auditory brainstem response threshold is at least 40 dB higher than the average control value of ~60 dB
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• hearing loss does not require loss of primary sensory cells, either the outer or inner hair cells
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nervous system
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• eventually the near complete loss of hair cells, first the outer hair cells and then the inner hair cells
|
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• vasculature of the cerebellum is noticeably sparser than controls at 30 days of age and very sparse and irregular at 6 months
• progressive cerebellar degeneration starting around 3rd postnatal week
|
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• dramatic loss of Purkinje cells and vacuolization
• apoptosis not observed in Purkinje cells but cells are lost progressively through adulthood
|
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• dramatic loss of granule cells and vacuolization
• massive apoptosis of granule cells starting between 14 and 19 days of age
• 50X more apoptosis in the cerebellum at 19 days of age
• apoptosis drops off greatly at 30 days of age
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• hypocellular cerebellum but cerebellar architecture normal
|
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• abnormal astroglial activation in adults
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cardiovascular system
|
• the two intraretinal capillary beds fail to develop
• major arteries and veins on the retina are enlarged and tortuous
• arteriolar arborization is diminished
• increased density of small vessels in nerve fiber layer
• many retinal blood vessels are fenestrated
|
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• enlarged blood vessels in the stria vascularis
• no identifiable blood vessels at 11 months of age
|
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• female homozygotes display disrupted vascular development of the corpora luteum
• markers of vascular cell function are reduced in ovaries of mutant female mice following natural mating
|
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• delayed superficial blood vessel growth in retina
• reduced vascular density in retina
|
|
• small hemorrhages frequent in cerebellum
(J:107732)
• extensive blood leakage in retina
(J:328283)
|
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• small hemorrhages frequent in retina
|
vision/eye
|
• the two intraretinal capillary beds fail to develop
• major arteries and veins on the retina are enlarged and tortuous
• arteriolar arborization is diminished
• increased density of small vessels in nerve fiber layer
• many retinal blood vessels are fenestrated
|
|
• small hemorrhages frequent in retina
|
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• delayed superficial blood vessel growth
• reduced vascular density
• extensive blood leakage
|
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• hyaloid blood vessels fail to regress or regression is delayed 1-2 weeks
|
digestive/alimentary system
|
• loss of skeletal muscle on lower 1/4 of esophagous to as much as the entire esophagus
• no motor end plates along the lower portion of the esophagus
|
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• desquamination of the esophageal epithelium
|
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• progressive enlargement of the esophagus apparent at 8 days of age but not at birth
|
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• defective esophageal peristalsis
• defective function of the gastric sphincter
|
muscle
|
• muscle fibers with smaller diameter but otherwise normal
|
pigmentation
|
• light black or silver coat color
|
reproductive system
| N |
• adult female homozygotes exhibit normal mating behavior relative to wild-type and heterozygous littermates
• following superovulation, female homozygotes produce an equal number of fertilized oocytes as their wild-type and heterozygous littermates
• immature mutant ovaries show normal follicular development and normal responses to gonadotropin stimulation during development to the preovulatory stage
|
 |
• whereas luteal cells in day 5.5 pregnant wild-type ovaries display cellular hypertrophy, luteal cells in day 5.5 non-pregnant mutant ovaries appear disorganized and display a lower cytoplasmic to nuclear ratio
• in mutant ovaries, expression of luteal cell-specific mRNAs is reduced as early as day 1.5 pc and remains low on day 5.5 pc
|
|
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• at 8 weeks of age, corpora lutea are variably present or absent in ovaries of some female mutant mice
• analysis of mutant ovaries from timed mating pairs shows that by day 7.5 pc, corpora lutea are not discernible, indicating that formation of functional corpora lutea is impaired
• on day 1.5 pc, mutant corpora lutea exhibit a thick, dense collagen IV network that is significantly less filamentous and punctate than that observed in wild-type corpora lutea, suggesting that vessel arborization is reduced during luteinization
• on day 1.5 pc, mutant corpora lutea exhibit clear signs of apoptosis, as indicated by the presence of activated caspase 3
|
|
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• after natural mating, some female homozygotes exhibit absence of corpora lutea
|
|
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• mutant ovaries collected at days 1.5, 5.5, and 7.5 pc display an altered histological appearance, reduced expression luteal cell-specific mRNAs, and distinct structural abnormalities within the vascular network, indicative of impaired luteal cell function
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• analysis of ovaries from timed mating pairs indicates that female homozygotes exhibit no implantation sites on days 5.5 and 7.5 pc
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• when mated to wild-type males, female homozygotes fail to become pregnant and produce offspring
|
 |
• preliminary observations suggest that male homozygotes appear to be infertile
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homeostasis/metabolism
|
• on day 1.5 post-coitum (pc), serum progesterone levels are reduced by 50% in female mutant mice relative to wild-type females, and decrease dramatically on days 5.5 and 7.5 pc with no evidence of implantation
• in contrast, no significant differences are observed in serum prolactin levels between female mutant and wild-type mice on day 5.5 pc
|
endocrine/exocrine glands
|
|
• whereas luteal cells in day 5.5 pregnant wild-type ovaries display cellular hypertrophy, luteal cells in day 5.5 non-pregnant mutant ovaries appear disorganized and display a lower cytoplasmic to nuclear ratio
• in mutant ovaries, expression of luteal cell-specific mRNAs is reduced as early as day 1.5 pc and remains low on day 5.5 pc
|
|
|
• at 8 weeks of age, corpora lutea are variably present or absent in ovaries of some female mutant mice
• analysis of mutant ovaries from timed mating pairs shows that by day 7.5 pc, corpora lutea are not discernible, indicating that formation of functional corpora lutea is impaired
• on day 1.5 pc, mutant corpora lutea exhibit a thick, dense collagen IV network that is significantly less filamentous and punctate than that observed in wild-type corpora lutea, suggesting that vessel arborization is reduced during luteinization
• on day 1.5 pc, mutant corpora lutea exhibit clear signs of apoptosis, as indicated by the presence of activated caspase 3
|
|
|
• after natural mating, some female homozygotes exhibit absence of corpora lutea
|
integument
|
• light black or silver coat color
|
cellular
|
|
• whereas luteal cells in day 5.5 pregnant wild-type ovaries display cellular hypertrophy, luteal cells in day 5.5 non-pregnant mutant ovaries appear disorganized and display a lower cytoplasmic to nuclear ratio
• in mutant ovaries, expression of luteal cell-specific mRNAs is reduced as early as day 1.5 pc and remains low on day 5.5 pc
|
Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
| exudative vitreoretinopathy | DOID:0050535 |
OMIM:PS133780 |
J:328283 | |
| Norrie disease | DOID:0060844 |
OMIM:310600 |
J:107732 | |
