Analysis Tools
mortality/aging
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• fewer homozygotes generated from heterozygous intercrosses are found at weaning (22% vs expected 25%)
• however, normal Mendelian ratios and normal-appearing mutant embryos are detected from E12.5 to E18.5
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reproductive system
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• male homozygotes show reduced numbers of spermatogenic precursors at various stages of development relative to wild-type males
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• at 6 weeks of age, mutant seminiferous tubules display consistently larger numbers of multinucleated giant cells than wild-type tubules
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• at 6 weeks of age, male homozygotes display greater numbers of TUNEL-positive (apoptotic) postmeiotic spermatids than wild-type or heterozygous mice
• however, no consistent reduction is noted in the number of spermatogonial progenitors, as detected by GCNA staining
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• at 6 weeks of age, male homozygotes show reduced eosinophilic material in the lumen of seminiferous tubules, indicating decreased numbers of mature sperm
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• at 6 weeks of age, mutant seminiferous tubules display consistently larger numbers of multinucleated giant cells than wild-type tubules
• male homozygotes exhibit significantly higher histopathologic scores for testicular degeneration at all ages examined (6-, 7, 8-, and 20 weeks of age)
• the nuclei present in giant cells appear to be derived from spermatids at various stages of maturation
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• at 6 to 7 weeks of age, male homozygotes exhibit significantly lower testicular weights than age-matched wild-type control males
• however, no differences in testicular weights are noted at 8-, 20- and 24 weeks of age, despite high histopathologic scores
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• homozygotes display testicular atrophy associated with increased apoptosis of germ cells
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• although germ cell development is clearly impaired, mutant sperm counts are sufficient to maintain fertility
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• at 6 weeks of age, male homozygotes display fewer mature sperm in the epidiymides than wild-type males
• however, normal testicular weights and sperm counts are detected at >6 weeks of age
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endocrine/exocrine glands
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• at 6 weeks of age, male homozygotes show reduced eosinophilic material in the lumen of seminiferous tubules, indicating decreased numbers of mature sperm
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• at 6 weeks of age, mutant seminiferous tubules display consistently larger numbers of multinucleated giant cells than wild-type tubules
• male homozygotes exhibit significantly higher histopathologic scores for testicular degeneration at all ages examined (6-, 7, 8-, and 20 weeks of age)
• the nuclei present in giant cells appear to be derived from spermatids at various stages of maturation
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• at 6 to 7 weeks of age, male homozygotes exhibit significantly lower testicular weights than age-matched wild-type control males
• however, no differences in testicular weights are noted at 8-, 20- and 24 weeks of age, despite high histopathologic scores
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• homozygotes display testicular atrophy associated with increased apoptosis of germ cells
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hematopoietic system
| N |
• homozygotes display normal peripheral blood counts and a normal frequency of lymphoid progenitors relative to wild-type controls
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• frequency of early progenitor (CFU-GEMM) colonies is severely reduced in 50% of homozygotes and normal in the remaining 50%
• however, frequency of clonogenic hematopoietic progenitors, BFU-E, and CFU-GM, is normal
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vision/eye
| N |
• homozygotes do not exhibit microphthalmia
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homeostasis/metabolism
| N |
• male homozygotes display no significant differences in serum FSH, LH, or prolactin levels relative to wild-type controls
• in addition, seminal vesicle weights, which are used as surrogate markers for serum testosterone, remain unaffected
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behavior/neurological
| N |
• homozygotes do not develop any overt neurologic symptoms in the first year of life
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cellular
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• male homozygotes show reduced numbers of spermatogenic precursors at various stages of development relative to wild-type males
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• at 6 weeks of age, male homozygotes display fewer mature sperm in the epidiymides than wild-type males
• however, normal testicular weights and sperm counts are detected at >6 weeks of age
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• at 6 weeks of age, mutant seminiferous tubules display consistently larger numbers of multinucleated giant cells than wild-type tubules
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• at 6 weeks of age, male homozygotes display greater numbers of TUNEL-positive (apoptotic) postmeiotic spermatids than wild-type or heterozygous mice
• however, no consistent reduction is noted in the number of spermatogonial progenitors, as detected by GCNA staining
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