Analysis Tools
mortality/aging
| N |
• surprisingly, homozygotes are viable with no obvious defects in major organ histology
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cellular
| N |
• no signs of significant double-strand break (DSB) repair defects in cell populations where developmentally programmed DSBs occur, including spermatocytes, oocytes, T cells and B cells
• normal sensitivity to the DNA crosslinking agent mitomycin C (MMC), as shown by survival rate at 21 days post i.p. injection
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• 5-fold reduction in total sperm count
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• aberrant head and tail morphologies in sperm from total epididymides
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• numerous sperm tail abnormalities
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• midpieces folded back against the sperm tail are observed
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• frequent narrowing of the sperm annulus
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• coiling of the sperm tail around the head is observed
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• two sperm tails are observed
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• all sperm lack a normal hook typical of wild-type sperm heads
• sperm heads folded back against the tail are observed
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• frequent bi-nucleate round spermatids and bi-nucleate elongating spermatids, often with a single acrosome stretching over both nuclei
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• high frequency of multi-nucleate cells in seminiferous tubules of various stages
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• modest but significant increase in the average number of apoptotic cells per seminiferous tubule with a 3-fold increase in the % of tubule sections with one or more TUNEL+ apoptotic cells
• TUNEL+ cells are scattered throughout tubule sections irrespective of stage
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• near absence of motile sperm; only a few twitching movements that fail to support forward progression
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reproductive system
 N |
• female homozygotes are fertile and show abundant oocytes in primordial and growing follicles at 3 months of age, although slightly reduced in number relative to wild-type controls
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• high frequency of multi-nucleate cells in seminiferous tubules of various stages
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• modest but significant increase in the average number of apoptotic cells per seminiferous tubule with a 3-fold increase in the % of tubule sections with one or more TUNEL+ apoptotic cells
• TUNEL+ cells are scattered throughout tubule sections irrespective of stage
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• severe defects in sperm development, most likely due to massively perturbed gene expression in spermatocytes and round spermatids; misregulation is already detected by late prophase, i.e. well before overt cellular defects
• however, spermatogenesis-associated changes in chromatin protein composition are relatively normal
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• 5-fold reduction in total sperm count
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• aberrant head and tail morphologies in sperm from total epididymides
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• numerous sperm tail abnormalities
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• midpieces folded back against the sperm tail are observed
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• frequent narrowing of the sperm annulus
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• coiling of the sperm tail around the head is observed
|
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• two sperm tails are observed
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• all sperm lack a normal hook typical of wild-type sperm heads
• sperm heads folded back against the tail are observed
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• frequent bi-nucleate round spermatids and bi-nucleate elongating spermatids, often with a single acrosome stretching over both nuclei
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• highly pleiotropic defects in spermatid development
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• some stage IX seminiferous tubules exhibit spermiation failure as shown by mature sperm retention, unlike in wild-type controls
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• caput epididymides are devoid of mature sperm
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• cauda epididymides contain only debris and degenerating, mostly round cells that likely slough from the seminiferous tubules
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• male homozygotes bred with wild-type females for 8 weeks fail to produce pups despite the presence of copulatory plugs
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• intracytoplasmic sperm injection (ICSI) using mutant epididymal sperm fails to spontaneously activate oocytes, and even after artificial activation, rarely yields embryos reaching the blastocyst stage
• however, injection of nuclei from mutant round spermatids into wild-type oocytes, followed by artificial activation, supports embryo formation to the blastocyst stage
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• near absence of motile sperm; only a few twitching movements that fail to support forward progression
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endocrine/exocrine glands
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• modest but significant increase in the average number of apoptotic cells per seminiferous tubule with a 3-fold increase in the % of tubule sections with one or more TUNEL+ apoptotic cells
• TUNEL+ cells are scattered throughout tubule sections irrespective of stage
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