Analysis Tools
nervous system
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• at 8 to 12 weeks of age, apoptotic cells are present in the entire cortex but are most prominent in neurons of layers II/III
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• cortical neurons treated with oxidative stress inducing agents (H2O2 or NMDA-type glutamate antagonist MK-801) show enhanced cell death compared to wild-type controls
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• at 8 weeks of age levels of inflammatory cytokines and activated microglia are increased
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• at 8 to 12 weeks of age, display prominent neuronal degeneration in the cerebral cortex and cerebellum
• apoptotic cells are present in the entire cortex but are most prominent in neurons of layers II/III
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cellular
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• TEM analysis of sperm revealed decreased mitochondrial electron density and swollen mitochondria in 8-week-old testes
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• swollen
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• at P10, testicular H&E staining showed an increased number of spermatocytes, while immunofluorescence showed a significantly higher ratio of SYCP3+ and DDX4+ cells than in wild-type testes
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• at P10, testes show a significantly higher number of CDH1+ (undifferentiated spermatogonia) and KIT+ (differentiating spermatogonia) germ cells per tubule than wild-type testes
• enhanced proliferation and differentiation of spermatogonial stem cells (SSCs) leads to exhaustion of EpCAM+ SSCs by 10 months of age
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• at 8 weeks of age, the number of ACRV1+ germ cells (spermatids and spermatozoa) per tubule is significantly lower than that in wild-type testes; the protein level of acrosin (an acrosome marker) is reduced
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• at 8 weeks of age, caudal epididymal sperm concentration is significantly lower than that in wild-type males
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• 8-week-old testes exhibit swollen mitochondria
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• at 8 weeks of age, TUNEL shows significantly increased germ cell apoptosis esp. in elongating/elongated spermatids; increased protein expression of BAX and cleaved-caspase-3 is observed
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• at 8 to 12 weeks of age, apoptotic cells are present in the entire cortex but are most prominent in neurons of layers II/III
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• cortical neurons treated with oxidative stress inducing agents (H2O2 or NMDA-type glutamate antagonist MK-801) show enhanced cell death compared to wild-type controls
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• at 8 weeks of age, sperm forward motility (%) is significantly lower than that in wild-type males
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• at 8 weeks of age, sperm motility (%) is significantly lower than that in wild-type males
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• at P10, testes show a significantly higher number of Ki67+ cells and phosphorylation-histone-H3+ cells per tubule than wild-type testes
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• mitochondrial impairment
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• testicular redox imbalance persists through adulthood with decreased NADPH/NADP and GSH/glutathione disulfide (GSSG) ratios at 8 weeks of age
• at P10, testes show marked redox imbalance with a decreased NADPH/NADP ratio
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• at 4 weeks of age multiple antioxidant defense genes are upregulated in the cortex and cerebellum indicative of oxidative stress
(J:214805)
• at 8 to 12 weeks of age accumulation of ROS and lipid peroxidation are seen in the cortex
(J:214805)
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• at 8 weeks of age, spermatozoa exhibit significantly increased intracellular reactive oxygen species (ROS) and malondialdehyde (MDA) levels, indicating oxidative stress
(J:324139)
• at P10, testes show significantly increased dihydroethidium-labeled ROS accumulation and a decreased NADPH/NADP ratio
(J:324139)
• at 8 weeks of age, testes show increased 4-hydroxy-2-nonenal (4-HNE), MDA and protein carbonyl content with widespread gammaH2AX+ labeling in elongating/elongated spermatids, indicating oxidative damage
(J:324139)
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homeostasis/metabolism
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• males exhibit normal serum testosterone levels at P10 and at 8 weeks of age
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• cortical neurons treated with oxidative stress inducing agents (H2O2 or NMDA-type glutamate antagonist MK-801) show enhanced cell death compared to wild-type controls
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reproductive system
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• at P10, testes show a significantly higher number of CDH1+ (undifferentiated spermatogonia) and KIT+ (differentiating spermatogonia) germ cells per tubule than wild-type testes
• enhanced proliferation and differentiation of spermatogonial stem cells (SSCs) leads to exhaustion of EpCAM+ SSCs by 10 months of age
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• at 8 weeks of age, the number of ACRV1+ germ cells (spermatids and spermatozoa) per tubule is significantly lower than that in wild-type testes; the protein level of acrosin (an acrosome marker) is reduced
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• at 8 weeks of age, TUNEL shows significantly increased germ cell apoptosis esp. in elongating/elongated spermatids; increased protein expression of BAX and cleaved-caspase-3 is observed
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• at P10, testes show a significant increase in the % of SYCP3+ seminiferous tubules and of SYCP3+ germ cells per tubule, and a higher number of phosphorylation-histone H3+ cells per tubule than wild-type testes
• at 8 weeks of age, seminiferous tubules show a reduced thickness of the germ cell layers with an enlarged central lumen
• however, the number and morphology of Leydig and Sertoli cells is normal
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• at 8 weeks of age, testis weight-to-body weight ratio is significantly lower than in wild-type males
• however, adult body weight is normal
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• at P10, testis weight-to-body weight ratio is significantly higher than in wild-type males
• however, juvenile body weight is normal
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• 8-week-old males show mild testicular atrophy
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• at 8 weeks of age, seminiferous tubules show a significant reduction in the number of spermatids and spermatozoa and a lower Johnsen's score than in wild-type controls, indicating impaired spermatogenesis
• however, the sequential progression of spermatogenesis is normal
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• TEM analysis of sperm revealed decreased mitochondrial electron density and swollen mitochondria in 8-week-old testes
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• swollen
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• at 8 weeks of age, caudal epididymal sperm concentration is significantly lower than that in wild-type males
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• at P10, testicular H&E staining showed an increased number of spermatocytes, while immunofluorescence showed a significantly higher ratio of SYCP3+ and DDX4+ cells than in wild-type testes
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• at P10, testes show a significantly higher number of Ki67+ cells and phosphorylation-histone-H3+ cells per tubule than wild-type testes
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• at 8 weeks of age, the cauda epididymis contains significantly fewer mature spermatozoa than in wild-type controls
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• when mated with wild-type females, 6-week-old males produce significantly fewer pups per litter than wild-type controls
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• when mated with wild-type females, 6-week-old males produced significantly fewer litters than wild-type controls over a 3-month period; only 23.8% of males produced 2 litters and none produced 3 litters
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• at 8 weeks of age, spermatozoa exhibit significantly increased intracellular reactive oxygen species (ROS) and malondialdehyde (MDA) levels, indicating oxidative stress
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• at 8 weeks of age, sperm forward motility (%) is significantly lower than that in wild-type males
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• at 8 weeks of age, sperm motility (%) is significantly lower than that in wild-type males
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endocrine/exocrine glands
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• at P10, testes show a significant increase in the % of SYCP3+ seminiferous tubules and of SYCP3+ germ cells per tubule, and a higher number of phosphorylation-histone H3+ cells per tubule than wild-type testes
• at 8 weeks of age, seminiferous tubules show a reduced thickness of the germ cell layers with an enlarged central lumen
• however, the number and morphology of Leydig and Sertoli cells is normal
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• at 8 weeks of age, testis weight-to-body weight ratio is significantly lower than in wild-type males
• however, adult body weight is normal
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• at P10, testis weight-to-body weight ratio is significantly higher than in wild-type males
• however, juvenile body weight is normal
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• 8-week-old males show mild testicular atrophy
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immune system
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• at 8 weeks of age levels of inflammatory cytokines and activated microglia are increased
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