Phenotypes associated with this allele
mortality/aging
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• mice are born alive and survive for at least several weeks but die of fatal bleeding as a result of bleeding diathesis, injury and pregnancy
• when kept separately without mating, female mice survive significantly longer than male mice
• male mice begin to die from day 27 after birth, and all males die within 80 days after birth
• female mice begin to die from day 39 after birth and 7 out of 11 (63.6%) survive longer than 100 days, unless they become pregnant
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• pregnancy causes fatal vaginal and uterine bleeding
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cardiovascular system
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• dissection of pregnant female mice just after death revealed uterine bleeding
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• dissection of pregnant female mice just after death revealed vaginal bleeding
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• at 9 weeks of age, massive subcutaneous bleeding is noted even before death
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homeostasis/metabolism
hematopoietic system
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• mice appear to die of anemia secondary to bleeding
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integument
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• at 9 weeks of age, massive subcutaneous bleeding is noted even before death
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reproductive system
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• dissection of pregnant female mice just after death revealed uterine bleeding
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• dissection of pregnant female mice just after death revealed vaginal bleeding
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mortality/aging
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N |
• none of the control heterozygotes died within the 100 days of the observation period
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| Find Mice |
Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Ggcxtm1Sinos mutation
(1 available);
any
Ggcx mutation
(36 available)
Tg(AMH-cre)#Sinos mutation
(0 available)
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reproductive system
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N |
• female mice exhibit normal reproductive ability
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• concentration of epididymal spermatozoa is significantly decreased at 4 months of age
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• percentage of morphologically abnormal spermatozoa with disordered flagella and sperm heads (e.g. coiled tails, bent sperm necks, and bent or unclear sperm heads) are significantly increased
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• disordered sperm flagella including round tails are observed
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• bent sperm midpieces are observed
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• coiled sperm tails are observed
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• bent or unclear sperm heads are observed
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• TEM revealed multinuclear spermatids with chromatin aggregation, nuclear fragmentation, vacuoles, and destroyed organelles
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• number of TUNEL+ germ cells per seminiferous tubule is significantly increased at 2, 4 and 8 months of age, indicating apoptotic degeneration of spermatids and spermatocytes
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• large TUNEL+ spermatocytes are observed in the testes at 2, 4 and 8 months of age
• Bax mRNA expression levels and Bax/Bcl2 ratios are significantly increased at 8 months of age
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• percentage of irregularly moving sperm cells is drastically increased
• however, no defect in sperm capacitation is observed
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• percentage of normal hyperactive sperm cells is reduced to half of that in control testes
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• testicular histology is drastically abnormal at 4 and 8 months, but not at 2 months of age
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• large multinuclear spermatids and intercellular space are observed at 4 months of age
• large clear lumen regions with severely reduced spermatids are noted at 8 months of age
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• protein expression and localization of GJA1 (also known as Cx43) are disordered in Sertoli cells: Cx43-positive signals are slightly moved to the inner side of the seminiferous tubules at 4 months and their intensity is markedly reduced at 8 months
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• testes are significantly smaller at 2, 4 and 8 months of age
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• testis weight is significantly reduced at 2, 4 and 8 months of age
• however, serum testosterone levels are normal at all tested ages
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• testes show substantial atrophy in the seminiferous tubules at 4 and 8 months
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• males exhibit late-onset infertility with loss of reproductive ability noted at 3 and 6 months but not at 2 months of age
• however, copulatory plugs are observed in mated wild-type females
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cellular
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• concentration of epididymal spermatozoa is significantly decreased at 4 months of age
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• percentage of morphologically abnormal spermatozoa with disordered flagella and sperm heads (e.g. coiled tails, bent sperm necks, and bent or unclear sperm heads) are significantly increased
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• disordered sperm flagella including round tails are observed
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• bent sperm midpieces are observed
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• coiled sperm tails are observed
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• bent or unclear sperm heads are observed
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• TEM revealed multinuclear spermatids with chromatin aggregation, nuclear fragmentation, vacuoles, and destroyed organelles
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• number of TUNEL+ germ cells per seminiferous tubule is significantly increased at 2, 4 and 8 months of age, indicating apoptotic degeneration of spermatids and spermatocytes
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• large TUNEL+ spermatocytes are observed in the testes at 2, 4 and 8 months of age
• Bax mRNA expression levels and Bax/Bcl2 ratios are significantly increased at 8 months of age
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• percentage of irregularly moving sperm cells is drastically increased
• however, no defect in sperm capacitation is observed
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• percentage of normal hyperactive sperm cells is reduced to half of that in control testes
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endocrine/exocrine glands
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• large TUNEL+ spermatocytes are observed in the testes at 2, 4 and 8 months of age
• Bax mRNA expression levels and Bax/Bcl2 ratios are significantly increased at 8 months of age
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• testicular histology is drastically abnormal at 4 and 8 months, but not at 2 months of age
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• large multinuclear spermatids and intercellular space are observed at 4 months of age
• large clear lumen regions with severely reduced spermatids are noted at 8 months of age
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• protein expression and localization of GJA1 (also known as Cx43) are disordered in Sertoli cells: Cx43-positive signals are slightly moved to the inner side of the seminiferous tubules at 4 months and their intensity is markedly reduced at 8 months
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• testes are significantly smaller at 2, 4 and 8 months of age
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• testis weight is significantly reduced at 2, 4 and 8 months of age
• however, serum testosterone levels are normal at all tested ages
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• testes show substantial atrophy in the seminiferous tubules at 4 and 8 months
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| Find Mice |
Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Ggcxtm1Sinos mutation
(1 available);
any
Ggcx mutation
(36 available)
Tg(AMH-cre)#Sinos mutation
(0 available)
Tg(AMH-Gja1*)#Sinos mutation
(0 available)
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reproductive system
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N |
• mice exhibit normal male fertility at 2 and 8 months of age and show no significant alterations in testis size, testis weight and seminiferous tubule histology or in GJA1 (Cx43) protein distribution at 8 months of age relative to controls, indicating that GJA1 overexpression in Sertoli cells rescues the sterility and testicular pathology phenotypes observed in Sertoli cell-specific Ggcx conditional knockout mice
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Analysis Tools