mortality/aging
• mice are subviable with a marked variability in lifespans; however, mice that pass a critical stage before weaning are able to survive like wild-type and heterozygous littermates
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• over 70% of mice die embryonically or perinatally, with only 7% of homozygotes recovered at weaning
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growth/size/body
• surviving mice weigh significantly less than control littermates from 4 to 12 weeks of age
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• surviving mice display growth retardation
• however, at birth, pups appear indistinguishable from control littermates
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reproductive system
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• mice exhibit significantly fewer germ cells in the seminiferous tubules
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• very large multinucleated giant cells (MGCs), some larger than 50 um in diameter, are found lining the lumen of seminiferous tubules and consist of numerous round spermatids
• punctate DAZL signals are detected in the MGCs in the seminiferous tubule lumen
• patchy Tex14 staining is observed on the MGC membrane, suggesting disrupted ICBs as a cause of MGC formation
• however, large MGCs are absent in the epididymal lumen
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• TUNEL staining showed massive germ cell apoptosis; many of the large multinucleated giant cells (MGCs) lining the lumen of seminiferous tubules undergo apoptosis
• both the number of TUNEL+ apoptotic cells per seminiferous tubule and the % of TUNEL+ tubules are significantly increased
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• seminiferous tubules contain significantly fewer cells, with no elongated spermatids or spermatozoa found in the seminiferous epithelium
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small testis
(
J:339470
)
|
• testes appear smaller at 4 months of age
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|
• at 4 months of age, testis weight is significantly less than that in control males
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• round spermatids are present, but no elongated spermatids or mature spermatozoa are detected
• immunostaining of TEX14, an intercellular bridge (ICB) marker, showed very few punctate TEX14 signals in the seminiferous tubules, indicating defective ICB formation/stabilization; TEX14 puncta per nucleus is reduced by >50%
• TEX14 is found on the MGC membrane in an aberrant patchy pattern, indicating impaired ICB protein complex assembly and targeting
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azoospermia
(
J:339470
)
|
• males produce no sperm; cauda epididymis lumen contains cellular debris and round bodies (likely degenerative residual bodies or sloughed germ cells) but no normal spermatozoa
|
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• some of the DAZL-positive (also SCP3-positive) spermatocytes become disorganized and are found near the seminiferous tubule lumen
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• PNA staining appears as small punctate dots in the testicular germ cell layers and as large bright clusters within the MGCs at the lumen, indicating a spermatogenesis arrest at the round spermatid stage
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• adult male mice are infertile
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cellular
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• some of the DAZL-positive (also SCP3-positive) spermatocytes become disorganized and are found near the seminiferous tubule lumen
|
|
• mice exhibit significantly fewer germ cells in the seminiferous tubules
|
azoospermia
(
J:339470
)
|
• males produce no sperm; cauda epididymis lumen contains cellular debris and round bodies (likely degenerative residual bodies or sloughed germ cells) but no normal spermatozoa
|
|
• very large multinucleated giant cells (MGCs), some larger than 50 um in diameter, are found lining the lumen of seminiferous tubules and consist of numerous round spermatids
• punctate DAZL signals are detected in the MGCs in the seminiferous tubule lumen
• patchy Tex14 staining is observed on the MGC membrane, suggesting disrupted ICBs as a cause of MGC formation
• however, large MGCs are absent in the epididymal lumen
|
|
• TUNEL staining showed massive germ cell apoptosis; many of the large multinucleated giant cells (MGCs) lining the lumen of seminiferous tubules undergo apoptosis
• both the number of TUNEL+ apoptotic cells per seminiferous tubule and the % of TUNEL+ tubules are significantly increased
|
endocrine/exocrine glands
|
• seminiferous tubules contain significantly fewer cells, with no elongated spermatids or spermatozoa found in the seminiferous epithelium
|
small testis
(
J:339470
)
|
• testes appear smaller at 4 months of age
|
|
• at 4 months of age, testis weight is significantly less than that in control males
|
homeostasis/metabolism
• levels of ether-linked phosphatidylcholines (pPC) and ether-linked phosphatidylethanolamines (pPE) are essentially undetectable in the testes
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