Analysis Tools
cellular
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• germ cells at any stage are absent in males >6 months of age
• germ cells do not progress beyond meiosis I in mutant males
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azoospermia
(
J:68137
)
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• mature sperms are totally absent in epididymis of mutant males
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• clumps of dying spermatocytes are observed at 4 weeks in seminiferous tubules, and post-meiotic spermatids are absent
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nervous system
| N |
• peripheral nervous system is relatively unaffected
• oligodendrocyte cell bodies and axons do not show morphological alterations in proximity to the vacuolations; also, no problems in myelin compaction is observed in peripheral nerves or in diameters of cerebellar myelin sheaths not directly affected by vacuolation
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• barrier function is impaired at 8 months, but not at 5 weeks
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• prominent vacuolation in fiber tracts of cerebellum
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• prominent vacuolation in fiber tracts of internal capsule
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• vacuole-like holes in large fiber tracts of brainstem at 22 months, but not at 14 days of age
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• vacuolation most prominent in fiber tracts of cerebellum
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• vacuole-like holes throughout white matter at 22 months, but not at 14 days of age
(J:122365)
• vacuoles contain myelin sheets, and are surrounded by thin myelin sheaths
(J:122365)
• severe myelin vacuolization
(J:210308)
• white matter vacuolization
(J:282228)
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• myelin vacuolation visible in spinal cord at 22 months
(J:122365)
• severe myelin vacuolization
(J:210308)
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• disorganized by P10
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• at P10, development is impaired relative to wild-type; displaced photoreceptor cells are seen beneath retinal pigment epithelium
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• disorganization is apparent by P10; mice have shortened and whirled outer segments rather than parallel lines of outer segments with regular stacks of disks
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• vacuole-like holes in spinal cord at 22 months, but not at 14 days of age
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• absent Cl- currents in Bergmann glia
• cell capacitance is slightly increased in Bergmann glia
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• at 8 months, mutants but not wild-type mice show microglial activation in the brain; such activation is not apparent at 5 weeks
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• membrane capacitance is increased
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• reduction in conduction velocity is observed; latency between peaks I and III in the auditory pathway is increased at 5 and 12 weeks of age
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behavior/neurological
| N |
• mice do not show overt seizures, or increased sensitivity to fluorethyl which induces seizures
(J:68137)
• motor learning and coordination are similar to wild-type
(J:122365)
• mice have similar seizure susceptibilities as wild-type mice, on exposure to fluorethyl or pentylenetetrazol
(J:122365)
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reproductive system
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• germ cells at any stage are absent in males >6 months of age
• germ cells do not progress beyond meiosis I in mutant males
|
azoospermia
(
J:68137
)
|
|
• mature sperms are totally absent in epididymis of mutant males
|
|
|
• clumps of dying spermatocytes are observed at 4 weeks in seminiferous tubules, and post-meiotic spermatids are absent
|
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• at 3 weeks of age, tubules lack lumina, and contain predominantly Sertoli cells, few spermatogonia, and abnormal clusters of primary spermatocytes
• by 4 weeks, tubules are smaller than in wild-type, lack lumina, and are filled mainly by Sertoli cells with long cytoplasmic extensions
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• cells have abnormal cytoplasmic extensions
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• degeneration with markedly reduced diameters and obliterated lumina; lumina are filled with membranous extensions of abnormal Sertoli cells
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• at 2 weeks of age, germinal epithelium is disorganized
• markers of germ cell development such as proacosin binding protein and Ccna1 which can be detected in wild-type at 3 weeks are completely absent in males at any age
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• Sertoli cells lack chloride currents
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• relative numbers of interstitial Leydig cells is increased in males >6 months of age
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small testis
(
J:68137
)
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• noticeable by 3 weeks of age, testes of males are markedly reduced in size relative to wild-type
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• testicular degeneration
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• homozygous males produce no litters despite normal copulatory behavior and vaginal plug formation in females after mating
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vision/eye
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• disorganized by P10
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• at P10, development is impaired relative to wild-type; displaced photoreceptor cells are seen beneath retinal pigment epithelium
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• disorganization is apparent by P10; mice have shortened and whirled outer segments rather than parallel lines of outer segments with regular stacks of disks
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• at P14, the outer nuclear layer contains large numbers of pyknotic nuclei and cell number is decreased by ~50%
• thickness of ONL decreases over next few weeks, such that at P31 only one or two rows of photoreceptor nuclei are present; at P65, only a few nuclei remain
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• mice kept in darkness from P0 to P35 show similar retinal degeneration to mice exposed to light
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• transepithelial transport across retinal pigment epithelium at P36 is significantly reduced relative to wild-type; transepithelial voltages are reduced from -6 mV in controls to <0.5 mV, and short circuit current across RPE is reduced
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cardiovascular system
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• barrier function is impaired at 8 months, but not at 5 weeks
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endocrine/exocrine glands
| N |
• androgen levels and testosterone secretion by Leydig cells is similar to wild-type males
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• at 3 weeks of age, tubules lack lumina, and contain predominantly Sertoli cells, few spermatogonia, and abnormal clusters of primary spermatocytes
• by 4 weeks, tubules are smaller than in wild-type, lack lumina, and are filled mainly by Sertoli cells with long cytoplasmic extensions
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• cells have abnormal cytoplasmic extensions
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• degeneration with markedly reduced diameters and obliterated lumina; lumina are filled with membranous extensions of abnormal Sertoli cells
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• at 2 weeks of age, germinal epithelium is disorganized
• markers of germ cell development such as proacosin binding protein and Ccna1 which can be detected in wild-type at 3 weeks are completely absent in males at any age
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• Sertoli cells lack chloride currents
|
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• relative numbers of interstitial Leydig cells is increased in males >6 months of age
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small testis
(
J:68137
)
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• noticeable by 3 weeks of age, testes of males are markedly reduced in size relative to wild-type
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• testicular degeneration
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homeostasis/metabolism
| N |
• mutants show normal serum concentrations of electrolytes, creatine, and liver-derived enzymes, as well as gastic acidification
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• mice exhibit elevated plasma renin concentration
• however, mice exhibit unaltered plasma aldosterone levels
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immune system
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• at 8 months, mutants but not wild-type mice show microglial activation in the brain; such activation is not apparent at 5 weeks
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hematopoietic system
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• at 8 months, mutants but not wild-type mice show microglial activation in the brain; such activation is not apparent at 5 weeks
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