Analysis Tools
reproductive system
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• accumulation of autofluorescent material in ovaries, starting as early as 3-5 weeks (puberty), rapidly increasing after 5-7 weeks (sexually mature), and becoming massive at 15-20 weeks (reproductive peak), greatly expanding the interstitial tissue
• 3.2-fold faster accumulation of autofluorescent material relative to wild-type ovaries
• numerous spherical bodies emitting autofluorescence with diameters of 20-60 um
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• significantly fewer corpora lutea at 15-20 weeks (reproductive peak) relative to wild-type controls
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• numerous autofluorescence-emitting spherical bodies, each surrounded by cells resembling theca cells and containing degrading organelles, myelin figures and granulosa cell nuclei, indicating abnormally collapsing atretic follicles abundant with lipofuscin
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• significantly fewer total developing follicles at 15-20 weeks (reproductive peak), with marked decrease in type 3, 4, and 7 developing follicles relative to wild-type controls
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• accelerated ovarian aging and functional decline
• impaired disposal of atretic follicles, resulting in massive accumulation of tissue wastes abundant with aging-related catabolic wastes such as lipofuscin
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• average reproductive life span (age for last successful delivery of a litter) is shortened to two thirds of that in heterozygous littermates
• females deliver fewer litters than heterozygous littermates (3.15 +/- 0.61 versus 5.90 +/- 0.48) during their entire reproductive life span
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• upon equine chorionic gonadotropin/hCG-induced superovulation at 15-20 weeks, the number of ovulated eggs is reduced to 65% of age-matched wild-type controls
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behavior/neurological
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• fear-based passive avoidance tests show a higher re-entry rate into the dark chamber post electric shock training in 60-80 week old mice, suggesting a loss of short memory
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• in habituation tests, 60-80 week old mice do not show a decline in exploration activities post training as wild-type controls
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• mice show an age-related increase in vertical activity after 60 weeks of age
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• mice show an age-related increase in horizontal activity after 60 weeks of age
• however, older mice show no differences in motor function assessment on the RotaMex
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homeostasis/metabolism
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• mice show a decrease in autophagy as indicated by a reduction of LC3 at 40 weeks prior to the onset of neuron loss and an increase in ubiquitinated proteins
(J:251814)
• mice exhibit an accumulation of numerous vesicles or vacuoles in neural soma and neurites at 60 weeks of age with many of them double-membraned indicating abnormal accumulation of autophagosomes
(J:251814)
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• diminished autophagy in atretic follicles, as shown by greatly reduced ovarian LC3-II protein, absence of LC3+ subcellular autophagosomes, and appearance of autofluorescent lipofuscin
(J:232676)
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• mice fail to initiate the repair of rapidly increasing DNA double-strand breaks in stressed cortical and hippocampal neurons after an abrupt aging surge at 40 weeks of age
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endocrine/exocrine glands
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• accumulation of autofluorescent material in ovaries, starting as early as 3-5 weeks (puberty), rapidly increasing after 5-7 weeks (sexually mature), and becoming massive at 15-20 weeks (reproductive peak), greatly expanding the interstitial tissue
• 3.2-fold faster accumulation of autofluorescent material relative to wild-type ovaries
• numerous spherical bodies emitting autofluorescence with diameters of 20-60 um
|
|
|
• significantly fewer corpora lutea at 15-20 weeks (reproductive peak) relative to wild-type controls
|
|
|
• numerous autofluorescence-emitting spherical bodies, each surrounded by cells resembling theca cells and containing degrading organelles, myelin figures and granulosa cell nuclei, indicating abnormally collapsing atretic follicles abundant with lipofuscin
|
|
|
• significantly fewer total developing follicles at 15-20 weeks (reproductive peak), with marked decrease in type 3, 4, and 7 developing follicles relative to wild-type controls
|
|
|
• impaired disposal of atretic follicles, resulting in massive accumulation of tissue wastes abundant with aging-related catabolic wastes such as lipofuscin
• accelerated ovarian aging and functional decline
|
cellular
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• mice show a decrease in autophagy as indicated by a reduction of LC3 at 40 weeks prior to the onset of neuron loss and an increase in ubiquitinated proteins
(J:251814)
• mice exhibit an accumulation of numerous vesicles or vacuoles in neural soma and neurites at 60 weeks of age with many of them double-membraned indicating abnormal accumulation of autophagosomes
(J:251814)
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• diminished autophagy in atretic follicles, as shown by greatly reduced ovarian LC3-II protein, absence of LC3+ subcellular autophagosomes, and appearance of autofluorescent lipofuscin
(J:232676)
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• failed disposal of atretic follicles is associated with impaired migration of ovarian macrophages into atretic follicles
• no invasion of MHC class II IA+ macrophages (which invade early atretic follicles with apoptotic cells) or CD68+ macrophages (which invade atretic follicles after mid-atresia post-wave of apoptosis) is observed, unlike in wild-type controls
• development of autofluorescence in atretic follicles coincides with failed migration of CD68+ macrophages into the same location
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• mice fail to initiate the repair of rapidly increasing DNA double-strand breaks in stressed cortical and hippocampal neurons after an abrupt aging surge at 40 weeks of age
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nervous system
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• 7 of 8 mice show heavy deposition of abnormal tau, that is hyper-phosphorylated, paired helical fragment, and insoluble, in cortical and hippocampal neurons at 65-80 weeks of age
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• vacuoles are often seen in the neuronal soma and neurites of pyramid neurons in the cortex as early as 40 weeks of age
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• neurodegeneration is seen in the cerebral cortex and hippocampus after 60 weeks of age, with heavy loss of neurites/neurons resulting in the disappearance of normal cortical layers and of hippocampal apical dendrite tufts
• however, older mice show no differences in Purkinje cell density in cerebella
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• seen after 60 weeks of age
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immune system
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• failed disposal of atretic follicles is associated with impaired migration of ovarian macrophages into atretic follicles
• no invasion of MHC class II IA+ macrophages (which invade early atretic follicles with apoptotic cells) or CD68+ macrophages (which invade atretic follicles after mid-atresia post-wave of apoptosis) is observed, unlike in wild-type controls
• development of autofluorescence in atretic follicles coincides with failed migration of CD68+ macrophages into the same location
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hematopoietic system
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• failed disposal of atretic follicles is associated with impaired migration of ovarian macrophages into atretic follicles
• no invasion of MHC class II IA+ macrophages (which invade early atretic follicles with apoptotic cells) or CD68+ macrophages (which invade atretic follicles after mid-atresia post-wave of apoptosis) is observed, unlike in wild-type controls
• development of autofluorescence in atretic follicles coincides with failed migration of CD68+ macrophages into the same location
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mortality/aging
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• average reproductive life span (age for last successful delivery of a litter) is shortened to two thirds of that in heterozygous littermates
• females deliver fewer litters than heterozygous littermates (3.15 +/- 0.61 versus 5.90 +/- 0.48) during their entire reproductive life span
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Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
| Alzheimer's disease | DOID:10652 | J:251814 | ||
