Analysis Tools
mortality/aging
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• partial embryonic lethality at or near the time of gastrulation, between E7.5 and E13.5
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growth/size/body
heterotaxia
(
J:279003
)
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• 28% of mice exhibit heterotaxy of either the heart or stomach
|
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• 55% of mice exhibit situs inverus
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nervous system
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• 4-fold increase in lateral ventricular volume is seen in the brain
• however, mice do not present external signs of hydrocephaly
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• the third ventricle appears enlarged
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reproductive system
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• decrease in epididymal sperm cell count
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• sperm exhibit gross morphological defects, including numerous detached heads and tails, kinked necks, bent tails, stubby tails, abnormal heads, and cytoplasmic bulges attached to the tails
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• males exhibit impaired sperm tail development, starting with the assembly of the core microtubular structure within the tail
• sperm exhibit cytoplasmic bulges attached to the tails
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• sperm tail axonemes are shortened and there is a decrease in axoneme-associated protein localization to the sperm tail, indicating impaired maturation of the axoneme
• microtubules in sperm tails are present in parallel arrays in the proximal tail region but they do not form the canonical 9 + 2 axoneme arrangement; microtubules are singlets and are not paired and some seem to be incomplete tubules
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• impaired midpiece formation, with poorly assembled outer dense fibers
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• the mitochondrial sheath contains centrally located mitochondria, but they are not properly organized
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• the fibrous sheath are not properly organized and are scattered in various portions of the tail indicating a failure to assemble properly
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• sperm tails are spiraled
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• sperm exhibit numerous detached heads and tails
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• some sperm exhibit abnormal heads
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• sperm shows acrosomal irregularities with clusters of acrosomal granules instead of the cap structure, and at later stages in spermatogenesis, there are instances of irregularly shaped acrosomes surrounding nuclei
• acrosome caps in testes at stages VIII-XI are irregularly shaped instead of round, with a delicate appearance and at stage XII, there are few misshapen acrosomes displaying a molar tooth shape
• -however, most acrosomes on elongating spermatids appear normal
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• spermatids at stage IX display manchette and while the basal plate and capitulum are present in the neck, segmented columns are either absent or severely disrupted
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• marker analysis indicates a failure to complete spermiogenesis by the inability to form the outer dense fiber layer or assembly of the fibrous sheath and failure of sperm tail elongation
• however, spermatogenesis appears to be normal through early tail formation, including formation of the manchette with centrally located centrioles
|
|
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• sperm release into the lumen is impaired, with a smaller lumen area, an absence of sperm tails, and an increase in residual bodies
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cellular
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• MEFs show shorter cilia after induction of primary cilia formation
• after 2 hours of serum addition, but not after 6-24 hours, a higher percentage of MEFs retain their cilia, indicating impaired initial depolymerization of primary cilia
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|
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• decrease in epididymal sperm cell count
|
|
|
• sperm exhibit gross morphological defects, including numerous detached heads and tails, kinked necks, bent tails, stubby tails, abnormal heads, and cytoplasmic bulges attached to the tails
|
|
|
• males exhibit impaired sperm tail development, starting with the assembly of the core microtubular structure within the tail
• sperm exhibit cytoplasmic bulges attached to the tails
|
|
|
• sperm tail axonemes are shortened and there is a decrease in axoneme-associated protein localization to the sperm tail, indicating impaired maturation of the axoneme
• microtubules in sperm tails are present in parallel arrays in the proximal tail region but they do not form the canonical 9 + 2 axoneme arrangement; microtubules are singlets and are not paired and some seem to be incomplete tubules
|
|
|
• impaired midpiece formation, with poorly assembled outer dense fibers
|
|
|
• the mitochondrial sheath contains centrally located mitochondria, but they are not properly organized
|
|
|
• the fibrous sheath are not properly organized and are scattered in various portions of the tail indicating a failure to assemble properly
|
|
|
• sperm tails are spiraled
|
|
|
• sperm exhibit numerous detached heads and tails
|
|
|
• some sperm exhibit abnormal heads
|
|
|
• -however, most acrosomes on elongating spermatids appear normal
• sperm shows acrosomal irregularities with clusters of acrosomal granules instead of the cap structure, and at later stages in spermatogenesis, there are instances of irregularly shaped acrosomes surrounding nuclei
• acrosome caps in testes at stages VIII-XI are irregularly shaped instead of round, with a delicate appearance and at stage XII, there are few misshapen acrosomes displaying a molar tooth shape
|
|
|
• spermatids at stage IX display manchette and while the basal plate and capitulum are present in the neck, segmented columns are either absent or severely disrupted
|
Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
| male infertility | DOID:12336 | J:279003 | ||
