Analysis Tools
behavior/neurological
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• male homozygotes fail to show any mating behavior or vaginal plugs in the presence of wild-type females in estrus, or superovulated females
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cellular
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• group I of male homozygotes exhibit oligo-astheno-teratospermia
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• group I of male homozygotes exhibit oligo-astheno-teratospermia with distinct head and flagellum anomalies, including a hammer-like head shape
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• in addition to the proliferative defect, primary MEFs show a 33% increase in the G0/G1 population, and appear enlarged and flat indicating premature senescence
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• mutant MEFs exhibit a Trp53-dependent hypersensitivity (2.5- to 5-fold) to UV-induced cell death; removal of Trp53 overcomes the UV hypersensitivity
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• group II of male homozygotes contain sperm of normal morphology and concentration but display a significantly impaired sperm motility
• group I of male homozygotes exhibit oligo-astheno-teratospermia
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• primary MEFs exhibit a significant reduction in cell colony growth upon plating at low density
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• in contrast to primary cells, immortalized fibroblast cell lines show increased proliferation associated with higher cyclin D1 levels
• also, immortalized fibroblast cell lines have spindle-like morphology and tend to pile up at high cell densities
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• T cells from homozygous mutant mice hyperproliferate following mitogen induction with anti-CD3 plus anti-CD28 or with PMA plus ionomycin
• in contrast, the proliferation of mutant T cells in response to concanavalin A remains unaffected
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endocrine/exocrine glands
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• group I of sterile males shows a complete absence of flagella in the lumen of the seminiferous tubules
• in stage VII tubules, complete loss of flagella correlates with a significant reduction in the number of late spermatid heads
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growth/size/body
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• homozygotes are viable and healthy but exhibit a postnatal growth retardation relative to wild-type
• however, no gross abnormalities are observed in the kidney, brain, stomach, gut, heart, skin, or pituitary up to 18 months
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homeostasis/metabolism
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• mutant males display a significant increase in inhibin B levels and a corresponding decrease in FSH levels
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• homozygotes display a 30% reduction in total pituitary GH levels
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• homozygotes display a 30% reduction in circulating GH levels in serum
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immune system
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• homozygotes show no major changes in hematopoietic lineages or signs of severe infection
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• T cells from homozygous mutant mice hyperproliferate following mitogen induction with anti-CD3 plus anti-CD28 or with PMA plus ionomycin
• in contrast, the proliferation of mutant T cells in response to concanavalin A remains unaffected
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• mutant Th2 cells secrete higher amounts of both IL-4 and IL-10 relative to wild-type Th2 cells
• mutant Th2 cells also produce high levels of the Th1-specific cytokine IFN-gamma, which is also increased in polarized Th1 cells CD4+ T cells
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• following LPS/galactosamine treatment, homozygotes exhibit earlier lethality than wild-type; only 36% of homozygotes survive compared to 82% of wild-type
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• homozygotes are significantly sensitive to LPS-induced hepatitis, with nearly all hepatocyte nuclei showing signs of apoptosis; in contrast, little hepatocyte apoptosis is noted in wild-type
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reproductive system
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• female homozygotes show no severe reproductive defects and produce litters of normal size
• male homozygotes show no differences in testosterone levels or in the weight of seminal vesicles relative to wild-type
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• group II of male homozygotes contain sperm of normal morphology and concentration but display a significantly impaired sperm motility
• group I of male homozygotes exhibit oligo-astheno-teratospermia
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• group I of sterile males shows a complete absence of flagella in the lumen of the seminiferous tubules
• in stage VII tubules, complete loss of flagella correlates with a significant reduction in the number of late spermatid heads
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• homozygotes exhibit heterogeneous spermatogenic defects (group I and II)
• however, testicular weight is normal
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• group I of male homozygotes exhibit oligo-astheno-teratospermia
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• group I of male homozygotes exhibit oligo-astheno-teratospermia with distinct head and flagellum anomalies, including a hammer-like head shape
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• 25% of male homozygotes fail to produce any litters over a 2-month breeding period
• the remaining males display an age-dependent drop in fertility and cease to produce litters as they grow older
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liver/biliary system
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• homozygotes are significantly sensitive to LPS-induced hepatitis, with nearly all hepatocyte nuclei showing signs of apoptosis; in contrast, little hepatocyte apoptosis is noted in wild-type
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hematopoietic system
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• T cells from homozygous mutant mice hyperproliferate following mitogen induction with anti-CD3 plus anti-CD28 or with PMA plus ionomycin
• in contrast, the proliferation of mutant T cells in response to concanavalin A remains unaffected
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• mutant Th2 cells secrete higher amounts of both IL-4 and IL-10 relative to wild-type Th2 cells
• mutant Th2 cells also produce high levels of the Th1-specific cytokine IFN-gamma, which is also increased in polarized Th1 cells CD4+ T cells
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