Analysis Tools
mortality/aging
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• mice are born at expected Mendelian ratio, but 30% them die on the first day after birth
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growth/size/body
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• mice surviving to adulthood are smaller than wild-type
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• mice surviving to adulthood exhibit decreased body weight throughout their lives
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reproductive system
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• at 40 days and at 3 months of age, males show a 2- to 3-fold reduction in the number of sperm cells isolated from the caudal epididymis relative to wild-type controls
• however, spermatozoan morphology and sperm cell motility appear normal
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• at 6 months of age, secondary ovarian follicles exhibit gross disorganization of the granulosa layers with apparent cellular pyknosis
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• at 6 months of age, the lumen within a third of the seminiferous tubules is obstructed causing a net decrease in spermatozoan yield
• tubular lumen is obstructed even in early stages (stages I-II and VI), unlike the lumen of wild-type mice which is empty (stages IV and XI)
• however, mean seminiferous tubule diameter is not altered at 3-18 months of age
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• at 3 to 6 months of age, the architecture of the seminiferous epithelium is significantly altered
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• the basal region of Sertoli cells appears distended and focally disrupted, with an expansion of intercellular spaces between adjacent cells, indicating a severely compromised blood-testis barrier (BTB)
• at 6 months of age, immunolabeling of N-cadherin and connexin 43 (two molecules that contribute to BTB formation and are constituent proteins of adherens and gap junctions, respectively) is weaker and more diffuse than in wild-type seminiferous tubules
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• at 1 to 18 months of age, the number of Sertoli cells is significantly increased, leading to a decreased ratio between germ cells (pachytene spermatocytes or round spermatids) and Sertoli cells in seminiferous tubules
• however, differentiation of Sertoli cells appears normal
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• a biotin tracer injected under the tunica albuginea is able to diffuse in the lumen of seminiferous tubules, unlike in wild-type controls where it is blocked by an intact BTB
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• primary Sertoli cells isolated from mutant testes display a reduced ability to engulf fluorescent latex beads relative to wild-type cells, not due to a recognition defect of the latex particle
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• breeding of male and female heterozygotes results in a significantly reduced average number of pups per female per month (0.66 versus 0.8 for wild-type intercrosses)
• subfertility is even more prominent when male or female homozygotes are crossed to wild-type mice (0.39 and 0.35, respectively) or when homozygotes are intercrossed (0.33)
• however, vaginal plugs are daily observed in females after pairing, indicating normal sexual behavior
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endocrine/exocrine glands
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• at 6 months of age, secondary ovarian follicles exhibit gross disorganization of the granulosa layers with apparent cellular pyknosis
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• at 6 months of age, the lumen within a third of the seminiferous tubules is obstructed causing a net decrease in spermatozoan yield
• tubular lumen is obstructed even in early stages (stages I-II and VI), unlike the lumen of wild-type mice which is empty (stages IV and XI)
• however, mean seminiferous tubule diameter is not altered at 3-18 months of age
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• at 3 to 6 months of age, the architecture of the seminiferous epithelium is significantly altered
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• the basal region of Sertoli cells appears distended and focally disrupted, with an expansion of intercellular spaces between adjacent cells, indicating a severely compromised blood-testis barrier (BTB)
• at 6 months of age, immunolabeling of N-cadherin and connexin 43 (two molecules that contribute to BTB formation and are constituent proteins of adherens and gap junctions, respectively) is weaker and more diffuse than in wild-type seminiferous tubules
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• at 1 to 18 months of age, the number of Sertoli cells is significantly increased, leading to a decreased ratio between germ cells (pachytene spermatocytes or round spermatids) and Sertoli cells in seminiferous tubules
• however, differentiation of Sertoli cells appears normal
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• a biotin tracer injected under the tunica albuginea is able to diffuse in the lumen of seminiferous tubules, unlike in wild-type controls where it is blocked by an intact BTB
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immune system
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• primary macrophages differentiated from mutant bone marrow mononuclear cells show a 50% reduction in the number of engulfed beads per macrophage relative to wild type cells
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hematopoietic system
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• primary macrophages differentiated from mutant bone marrow mononuclear cells show a 50% reduction in the number of engulfed beads per macrophage relative to wild type cells
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cellular
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• at 40 days and at 3 months of age, males show a 2- to 3-fold reduction in the number of sperm cells isolated from the caudal epididymis relative to wild-type controls
• however, spermatozoan morphology and sperm cell motility appear normal
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• primary macrophages differentiated from mutant bone marrow mononuclear cells show a 50% reduction in the number of engulfed beads per macrophage relative to wild type cells
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