Analysis Tools
reproductive system
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• adult homozygotes exhibit a significant reduction in the number of maturing spermatocytes
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• homozygotes exhibit early apoptotic changes in early-mid pachytene spermatocytes that are often associated with significantly degenerated cells in the testis
• many germ cells display marked aggregation/margination of nuclear contents and early fragmentation of the cytoplasm
• ploidy analysis by flow cytometry confirmed that 70%-80% of primary spermatocytes are lost to apoptosis during prophase I of meiosis after chromosomal doubling
• male germ apoptosis precedes the onset of puberty and occurs during the first round of spermatogenesus in mutant mice
• moreover, the extent of spermatocyte apoptosis is not significantly altered in a p53-null background
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• however, both spermatogonia and Sertoli cells appear morphologically intact in all tubules examined
• most seminiferous tubules contain highly degenerated cells that cannot be staged
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• adult homozygotes display distortion of the seminiferous epithelium architecture
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• mutant testes exhibit relatively small tubules with open lumina due to a significant reduction in the number of maturing spermatocytes
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• mutant testes exhibit Leydig cell hyperplasia relative to wild-type testes
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small testis
(
J:58099
)
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• adult homozygotes display microrchidia
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• at >8 weeks of age, mutant testes weigh 43% of wild-type
• a 26% reduction in mutant testis weight is first evident at P14, after germ cells have entered the first round of spermatogenesis but prior to the onset of puberty
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• male homozygotes exhibit a nearly complete germ cell maturation arrest at the early-mid pachytene stage
• while many early-mid pachytene spermatocytes appeear to degenerate, the maturation arrest is not complete, as some late pachytene spermatocytes are still identifiable
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• most homozygotes contain frequent immature germ cells and negligible numbers of mature spermatozoa in their cauda epididymides
• however, a sufficient number of mature spermatozoa are still present for morphologcal analysis
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• spermatozoa obtained from mutant cauda epididymides are significantly reduced in number and display a variety of structural defects
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• mutant flagella are often sharply kinked, fragmented, or exhibit tightly coiled distal ends
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• frequently, mutant sperm heads are either detached completely or bent sharply back on the flagellum to obscure the acrosomal cap
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• 70%-80% of mutant primary spermatocytes fail to transgress the early-mid pachytene stage of meiotic prophase due to massive germ cell death
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• male, but not female, homozygotes are infertile
• occasional male homozygotes sire very small litters (4-5 pups) but never with the frequency of wild-type males
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endocrine/exocrine glands
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• however, both spermatogonia and Sertoli cells appear morphologically intact in all tubules examined
• most seminiferous tubules contain highly degenerated cells that cannot be staged
|
|
|
• adult homozygotes display distortion of the seminiferous epithelium architecture
|
|
|
• mutant testes exhibit relatively small tubules with open lumina due to a significant reduction in the number of maturing spermatocytes
|
|
|
• mutant testes exhibit Leydig cell hyperplasia relative to wild-type testes
|
small testis
(
J:58099
)
|
|
• adult homozygotes display microrchidia
|
|
|
• at >8 weeks of age, mutant testes weigh 43% of wild-type
• a 26% reduction in mutant testis weight is first evident at P14, after germ cells have entered the first round of spermatogenesis but prior to the onset of puberty
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homeostasis/metabolism
| N |
• adult male homozygotes display no significant differences in serum LH and FSH levels relative to wild-type males, as measured by radioimmunoassays
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cellular
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• spermatozoa obtained from mutant cauda epididymides are significantly reduced in number and display a variety of structural defects
|
|
|
• mutant flagella are often sharply kinked, fragmented, or exhibit tightly coiled distal ends
|
|
|
• frequently, mutant sperm heads are either detached completely or bent sharply back on the flagellum to obscure the acrosomal cap
|
|
|
• adult homozygotes exhibit a significant reduction in the number of maturing spermatocytes
|
|
|
• most homozygotes contain frequent immature germ cells and negligible numbers of mature spermatozoa in their cauda epididymides
• however, a sufficient number of mature spermatozoa are still present for morphologcal analysis
|
|
|
• homozygotes exhibit early apoptotic changes in early-mid pachytene spermatocytes that are often associated with significantly degenerated cells in the testis
• many germ cells display marked aggregation/margination of nuclear contents and early fragmentation of the cytoplasm
• ploidy analysis by flow cytometry confirmed that 70%-80% of primary spermatocytes are lost to apoptosis during prophase I of meiosis after chromosomal doubling
• male germ apoptosis precedes the onset of puberty and occurs during the first round of spermatogenesus in mutant mice
• moreover, the extent of spermatocyte apoptosis is not significantly altered in a p53-null background
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