Analysis Tools
mortality/aging
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• lethality is seen between 3 and 20 weeks of age
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• about half as many mice as expected are present at weaning however no reduction in numbers is detected at E18.5
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growth/size/body
skeleton
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• small extra bone present above C1 in 29% of homozygous mice
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• transformation of T7 to T8 and T13 to L1 are seen in 71% and 57% of homozygous mice, respectively
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• transformation of C1 to C2 and C7 to T1 are seen in 57% and 29% of homozygous mice, respectively
• partial transformation of C7 to T1 is seen in 43% of homozygous mice
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• transformation of L6 to S1 is seen in 86% of homozygous mice
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hematopoietic system
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• shift in the distribution of myeloid to B lymphoid cells resulting in an increased percentage of myeloid cells
• within the B cell population, loss of immature B cells is greater than the loss of mature B cells
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• decreased number of hematopoietic cells in the thymus, bone marrow and spleen
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reproductive system
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• over 50% of sperm exhibit severe malformations at 7 weeks of age
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• mitochondrial contents are significantly reduced in the sperm mitochondrial sheath
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• numerous sperm head defects are observed, including irregular, sharp and big heads
• several genes required for sperm shaping are significantly downregulated
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• sperm nucleus is detached from the acrosome
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• sperm exhibit nuclear condensation defects
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• germ cell counts are reduced in the seminiferous tubule epithelium at 7 weeks of age
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• CASA analysis of sperm counts in caudal epididymis revealed severe oligospermia at 7 weeks of age
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• male germ cell proliferation is severely reduced, as determined by Ki67 immunostaining in testicular sections
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• male germ cell apoptosis is markedly increased, as determined by a TUNEL assay in testicular sections
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• seminiferous tubule epithelium is highly disorganized at 7 weeks of age
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• seminiferous tubule diameters are reduced at 7 weeks of age
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• Leydig cell population (3betaHSD positive cells) is significantly reduced at 7 weeks of age
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small testis
(
J:286451
)
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• testis size is significantly smaller than that in wild-type controls at 7 weeks of age
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• testis weight is significantly reduced at 7 weeks of age
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• both p16 and p53 immunopositive cells in testis are significantly increased and the protein expression levels of p16, p19, p53 and p21 are markedly up-regulated in testis extracts from 7-week-old male mice
• reactive oxygen species (ROS) and (H2O2) levels are significantly increased whereas total antioxidant capacity and the expression levels of antioxidant enzyme genes (Gpx1, Gsr, Cat, Txnrd1) are decreased
• numbers of 8-OHdG positive cells and gammaH2AX positive cells are dramatically increased in testicular sections, indicating increased DNA damage
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• testosterone production is reduced and both mRNA and protein levels of Hsd3b1 (3betaHSD) and Hsd17b1 (17betaHSD) are significantly downregulated in testis extracts from 7-week-old male mice
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• round immature germ cell like cells are found in epididymal sections at 7 weeks of age
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• male mice mated with adult wild-type females of proven fertility for 1 month are unable to produce offspring, indicating complete male sterility
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cellular
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• over 50% of sperm exhibit severe malformations at 7 weeks of age
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• mitochondrial contents are significantly reduced in the sperm mitochondrial sheath
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• numerous sperm head defects are observed, including irregular, sharp and big heads
• several genes required for sperm shaping are significantly downregulated
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• sperm nucleus is detached from the acrosome
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• sperm exhibit nuclear condensation defects
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• germ cell counts are reduced in the seminiferous tubule epithelium at 7 weeks of age
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• CASA analysis of sperm counts in caudal epididymis revealed severe oligospermia at 7 weeks of age
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• impaired ability of serum-starved MEFs to re-enter the cell cycle
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• defect in asynchronous proliferation in MEFs
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• in MEFs
(J:134271)
• in mouse embryonic fibroblasts by passage 6
(J:198334)
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• male germ cell proliferation is severely reduced, as determined by Ki67 immunostaining in testicular sections
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• male germ cell apoptosis is markedly increased, as determined by a TUNEL assay in testicular sections
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• reactive oxygen species (ROS) and hydrogen peroxide (H2O2) levels are significantly increased whereas total antioxidant capacity and the expression levels of antioxidant enzyme genes (Gpx1, Gsr, Cat, Txnrd1) are decreased in testis extracts from 7-week-old male mice
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behavior/neurological
nervous system
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• all three layers are affected
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immune system
endocrine/exocrine glands
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• seminiferous tubule epithelium is highly disorganized at 7 weeks of age
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• seminiferous tubule diameters are reduced at 7 weeks of age
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• Leydig cell population (3betaHSD positive cells) is significantly reduced at 7 weeks of age
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small testis
(
J:286451
)
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• testis size is significantly smaller than that in wild-type controls at 7 weeks of age
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• testis weight is significantly reduced at 7 weeks of age
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• both p16 and p53 immunopositive cells in testis are significantly increased and the protein expression levels of p16, p19, p53 and p21 are markedly up-regulated in testis extracts from 7-week-old male mice
• reactive oxygen species (ROS) and (H2O2) levels are significantly increased whereas total antioxidant capacity and the expression levels of antioxidant enzyme genes (Gpx1, Gsr, Cat, Txnrd1) are decreased
• numbers of 8-OHdG positive cells and gammaH2AX positive cells are dramatically increased in testicular sections, indicating increased DNA damage
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• testosterone production is reduced and both mRNA and protein levels of Hsd3b1 (3betaHSD) and Hsd17b1 (17betaHSD) are significantly downregulated in testis extracts from 7-week-old male mice
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homeostasis/metabolism
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• serum testosterone levels are significantly reduced at 7 weeks of age
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• both mRNA and protein levels of Hsd3b1 (3betaHSD) and Hsd17b1 (17betaHSD) are significantly downregulated in testis extracts from 7-week-old male mice
• expression levels of antioxidant enzyme genes including Gpx1, Gsr, Cat, Txnrd1 are decreased in testis extracts
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