Analysis Tools
reproductive system
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• male homozygotes display abnormal sperm maturation in the proximal epididymis
• however, mutant testicular and epididymal structures exhibit normal development, and spermatozoa descending from the seminiferous tubules of the testis into the initial segment of the epididymis are morphologically normal
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• after exit from the initial epididymal segment, distinct tail abnormalities are increasingly observed during transit of sperm through the epididymal duct
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• some sperm mid-pieces show abnormal kinking and fraying of axonemal structures
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• unlike wild-type, most mutant spermatozoa exhibit a highly irregular mitochondrial helix in mid-piece sections of the sperm tail
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• ~51% of mutant spermatozoa from the cauda epididymidis display coiling of the tail with a variable degree of bending
• ~49% show normal straight tail morphology
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• 43% of mutant spermatozoa from the cauda epididymidis exhibit hairpin structures (180 degrees)
• hairpin morphology is completely reverted upon incubation in buffer containing mild detergents (0.1% Triton X-100), indicating cell volume dysregulation
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• 8% of mutant spermatozoa from the cauda epididymidis show slight angulations (<90 degrees)
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(J:55691)
• male infertility is associated with reduced expression of a sperm maturation protein (GPX4) in the epididymis
(J:84102)
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• mutant spermatozoa from the cauda epididymidis fail to regulate the intracellular osmotic pressure ("cell volume decrease")
• as a result, sperm fail to counteract water influx when released into hypo-osmotic conditions, causing cell swelling and coiling of the sperm tail
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• the % of motile mutant sperm is reduced to half the wild-type control value
• although curvilinear velocity and the amplitude of lateral head displacement remain normal, all other sperm analysis parameters are significantly reduced indicating ineffective forward progression
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behavior/neurological
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• contextual fear-conditioned learning deficits
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• homozygotes spent less time in the training quadrant and crossed the former platform position less often in probe trials compared to wild-type mice
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nervous system
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• corticospinal neurons are mislocalized to layers 4 and 6 of cerebral cortex
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• cortical layering disrupted, with neurons packed into tight horizontal layers
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• less foliated than wild-type
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• neurons in the dentate gyrus were very loosely packed
(J:55691)
• ectopic calbindin-positive cells are located mainly in the polymorph layer between the densely packed granule layers
(J:105699)
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• ectopic calbindin-positive cells are located mainly in the polymorph layer between the densely packed granule layers
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• at P21, markers for cortical layer 6 and subplate neurons have broadened expression, indicating that neurons are infiltrating layers closer to the cortical surface
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• abnormal aggregates of Purkinje cells and cortical neurons
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cellular
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• after exit from the initial epididymal segment, distinct tail abnormalities are increasingly observed during transit of sperm through the epididymal duct
|
|
|
• some sperm mid-pieces show abnormal kinking and fraying of axonemal structures
|
|
|
• unlike wild-type, most mutant spermatozoa exhibit a highly irregular mitochondrial helix in mid-piece sections of the sperm tail
|
|
|
• ~51% of mutant spermatozoa from the cauda epididymidis display coiling of the tail with a variable degree of bending
• ~49% show normal straight tail morphology
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|
|
• 43% of mutant spermatozoa from the cauda epididymidis exhibit hairpin structures (180 degrees)
• hairpin morphology is completely reverted upon incubation in buffer containing mild detergents (0.1% Triton X-100), indicating cell volume dysregulation
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|
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• 8% of mutant spermatozoa from the cauda epididymidis show slight angulations (<90 degrees)
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• in mutants, corticospinal neurons are resistant to lesion-induced cell death whereas ~40% of wild-type CSN die after CSN deafferentation at 1 month of age; at 4 months, survival ratio is similar
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• corticospinal neurons are mislocalized to layers 4 and 6 of cerebral cortex
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• the % of motile mutant sperm is reduced to half the wild-type control value
• although curvilinear velocity and the amplitude of lateral head displacement remain normal, all other sperm analysis parameters are significantly reduced indicating ineffective forward progression
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