reproductive system
• at P10, development to the preleptotene spermatocyte stage is severely disrupted, rendering predominantly Sertoli cells and type A spermatogonia in seminiferous tubules
• by P14 and P21, all spermatocyte stages from preleptotene to diplotene are severely depleted
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• at P7, mice have normal numbers of Sertoli cells and type A spermatogonia but start to show decreased numbers of intermediate/type B spermatogonia
• at P21, mice show a 2-fold reduction in the numbers of type A spermatogonia and a >3-fold reduction in the numbers of intermediate/type B spermatogonia per Sertoli cell
• at 5 months, mice contain ~60% as many type A spermatogonia and ~15% as many intermediate/type B spermatogonia as in wild-type controls per Sertoli cell
• histology revealed a degenerative defect in the progression of differentiating type A spermatogonia into type B spermatogonia, consistent with increased numbers of abnormal differentiating type A-like spermatogonia on the tubular basement membrane at all ages examined
• degenerating cells resemble type A2 spermatogonia and accumulate in M-phase prior to death
• at 2 months of age, the ratio of undifferentiated type A spermatogonia (DAZL+/PLZF+) to differentiating type A spermatogonia (DAZL+/PLZF-) is twice normal levels
• in culture, undifferentiated type A spermatogonia derived from 10-day-old mice proliferate normally but show a >3-fold reduction in Kit expression relative to wild-type controls
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• at 8 weeks of age, a severe reduction in the number of spermatogonia and spermatocytes is noted in seminiferous tubules
• at 1, 2, and 5 months of age, mice display no spermatocytes or spermatids but contain undifferentiated and differentiating type A spermatogonia
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small testis
(
J:220953
)
• at 8 weeks of age, testes are clearly undersized
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• significant reduction in testis weight at P14, with the weight difference increasing over time
• at 8-16 weeks of age, average testis weight is 3 to 4 times less than that of wild-type or heterozygous controls
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• early onset of testicular atrophy, starting at 2 weeks of age
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• early spermatogenic block due to degeneration of differentiating type A spermatogonia, resulting in absence of meiotic and haploid germ cells in adult testes
• normal progression of differentiating type A spermatogonia into type B spermatogonia is disrupted
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• adult male mice are sterile but otherwise developmentally normal
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endocrine/exocrine glands
small testis
(
J:220953
)
• at 8 weeks of age, testes are clearly undersized
|
• significant reduction in testis weight at P14, with the weight difference increasing over time
• at 8-16 weeks of age, average testis weight is 3 to 4 times less than that of wild-type or heterozygous controls
|
• early onset of testicular atrophy, starting at 2 weeks of age
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cellular
• at P10, development to the preleptotene spermatocyte stage is severely disrupted, rendering predominantly Sertoli cells and type A spermatogonia in seminiferous tubules
• by P14 and P21, all spermatocyte stages from preleptotene to diplotene are severely depleted
|
• at P7, mice have normal numbers of Sertoli cells and type A spermatogonia but start to show decreased numbers of intermediate/type B spermatogonia
• at P21, mice show a 2-fold reduction in the numbers of type A spermatogonia and a >3-fold reduction in the numbers of intermediate/type B spermatogonia per Sertoli cell
• at 5 months, mice contain ~60% as many type A spermatogonia and ~15% as many intermediate/type B spermatogonia as in wild-type controls per Sertoli cell
• histology revealed a degenerative defect in the progression of differentiating type A spermatogonia into type B spermatogonia, consistent with increased numbers of abnormal differentiating type A-like spermatogonia on the tubular basement membrane at all ages examined
• degenerating cells resemble type A2 spermatogonia and accumulate in M-phase prior to death
• at 2 months of age, the ratio of undifferentiated type A spermatogonia (DAZL+/PLZF+) to differentiating type A spermatogonia (DAZL+/PLZF-) is twice normal levels
• in culture, undifferentiated type A spermatogonia derived from 10-day-old mice proliferate normally but show a >3-fold reduction in Kit expression relative to wild-type controls
|
• at 8 weeks of age, a severe reduction in the number of spermatogonia and spermatocytes is noted in seminiferous tubules
• at 1, 2, and 5 months of age, mice display no spermatocytes or spermatids but contain undifferentiated and differentiating type A spermatogonia
|