Analysis Tools
vision/eye
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• photoreceptors exhibit a significant reduction in connecting cilium length at 3, 6, and 9 months of age
• in addition, connecting cilia display a swollen upper part and disorganized microtubules (spreading of microtubule doublets in the proximal half)
• however, structures of basal bodies, adjacent daughter centrioles, and other organelles of inner segments are not altered
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• TEM analysis showed disorganized, sparse, and caduceus photoreceptor outer segment (OS) disks and widened OS bases at 3, 6, and 9 months of age
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• photoreceptors show aberrant organization of OS disks
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• light-induced translocation of cone arrestin from the inner cellular compartments to the outer segments (OS) of cone photoreceptors is slower and more limited than in heterozygous retinas
• however, distribution patterns of cone arrestin are normal in dark-adapted retinas
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• thickness of the retina outer nuclear layer (ONL) is reduced at 3, 9, and 12 months of age relative to age-matched heterozygotes
• reduction in ONL thickness becomes more evident with increasing age
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• scotopic a-wave amplitudes are reduced by approximately 13.6%, 39.1%, 40.8%, and 64.8% at 3, 6, 9, and 18 months of age, respectively, relative to age-matched heterozygotes
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• scotopic b-wave amplitudes are reduced by 19.9%, 30.5%, 35.6%, and 58.3% at 3, 6, 9, and 18 months of age, respectively, relative to age-matched heterozygotes
• photopic b-wave amplitudes are reduced by 39.4%, 39.8%, 52.8%, and 69.0% at 3, 6, 9, and 18 months, respectively
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reproductive system
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• despite male infertility, testis weight and testis/body weight are similar to those in heterozygous control males
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• CASA analysis showed a significant reduction in cauda epididymal sperm progressive motility
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• CASA analysis showed a significant reduction in cauda epididymal sperm motility relative to heterozygous control males
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• PAS staining showed scarce sperm flagella visible in the lumens of testes, with flagellar formation defects observed from stages I-III to stages VII-VIII
• very few spermatids reach maturity successfully and pass into the epididymis
• however, spermatocyte development is normal, suggesting that prophase of meiosis I is unaffected
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• CASA analysis showed a significant reduction in cauda epididymal sperm concentration relative to heterozygous control males
• H&E staining showed less spermatozoa in both caput and cauda epididymis than in age-matched control males
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• males exhibit multiple abnormalities in the sperm head and flagella
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• severely distorted sperm flagella are identified; 95.67% of total spermatozoa exhibit abnormal flagella, including absent, short, coiled, and/or multi-flagella
• triplet microtubules are found in both middle and principal pieces of sperm flagella, indicating abnormal elongation of centrioles during sperm flagella formation
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• sperm show complete derangement of outer dense fibers (ODFs)
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• sperm show scattered 9+2 microtubules, indicating axonemal defects
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• 82.61% of total spermatozoa exhibit abnormal necks
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• sperm show disordered mitochondria
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• short flagella are frequently observed
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• severely distorted sperm heads are identified; 92.10% of total spermatozoa exhibit abnormal heads
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• spermatids show defects in acrosome biogenesis and nuclei invagination
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• acrosomes are detached from the nuclear membrane
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• an abnormal nuclear constriction is noted at the site of perinuclear rings
• ectopic and asymmetric perinuclear rings are observed
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• testicular spermatids exhibit abnormal elongation of manchette structures
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• triplet microtubules, which normally exist only in proximal centrioles, are detected in both middle and principal pieces of the sperm flagella, suggesting centriole anomalies during spermiogenesis
• staining of centrioles and peri-centriole materials revealed a significant increase in centriole length
• testes show deformed spermatid nuclei, as indicated by abnormal club-shaped nuclear morphology of elongated spermatids starting at step 10 of spermiogenesis
• testicular spermatids exhibit abnormal elongation of manchette structures
• however, nuclear condensation is not affected
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• spermatids show defects in manchette formation leading to disordered manchette microtubules
• defective manchette formation results in abnormal nuclear shaping and sperm head formation
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• less spermatozoa are detected in the caput epididymis than in age-matched control males
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• matings between male homozygotes and wild-type females produce no offspring
• matings with heterozygous female mice for 3 months confirmed that male homozygotes are infertile
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nervous system
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• photoreceptors exhibit a significant reduction in connecting cilium length at 3, 6, and 9 months of age
• in addition, connecting cilia display a swollen upper part and disorganized microtubules (spreading of microtubule doublets in the proximal half)
• however, structures of basal bodies, adjacent daughter centrioles, and other organelles of inner segments are not altered
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• TEM analysis showed disorganized, sparse, and caduceus photoreceptor outer segment (OS) disks and widened OS bases at 3, 6, and 9 months of age
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• photoreceptors show aberrant organization of OS disks
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• light-induced translocation of cone arrestin from the inner cellular compartments to the outer segments (OS) of cone photoreceptors is slower and more limited than in heterozygous retinas
• however, distribution patterns of cone arrestin are normal in dark-adapted retinas
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cellular
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• photoreceptors exhibit a significant reduction in connecting cilium length at 3, 6, and 9 months of age
• in addition, connecting cilia display a swollen upper part and disorganized microtubules (spreading of microtubule doublets in the proximal half)
• however, structures of basal bodies, adjacent daughter centrioles, and other organelles of inner segments are not altered
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• CASA analysis showed a significant reduction in cauda epididymal sperm concentration relative to heterozygous control males
• H&E staining showed less spermatozoa in both caput and cauda epididymis than in age-matched control males
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• males exhibit multiple abnormalities in the sperm head and flagella
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• severely distorted sperm flagella are identified; 95.67% of total spermatozoa exhibit abnormal flagella, including absent, short, coiled, and/or multi-flagella
• triplet microtubules are found in both middle and principal pieces of sperm flagella, indicating abnormal elongation of centrioles during sperm flagella formation
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• sperm show complete derangement of outer dense fibers (ODFs)
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• sperm show scattered 9+2 microtubules, indicating axonemal defects
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• 82.61% of total spermatozoa exhibit abnormal necks
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• sperm show disordered mitochondria
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• short flagella are frequently observed
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• severely distorted sperm heads are identified; 92.10% of total spermatozoa exhibit abnormal heads
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• spermatids show defects in acrosome biogenesis and nuclei invagination
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• acrosomes are detached from the nuclear membrane
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• spermatids show defects in manchette formation leading to disordered manchette microtubules
• defective manchette formation results in abnormal nuclear shaping and sperm head formation
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• an abnormal nuclear constriction is noted at the site of perinuclear rings
• ectopic and asymmetric perinuclear rings are observed
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• testicular spermatids exhibit abnormal elongation of manchette structures
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• CASA analysis showed a significant reduction in cauda epididymal sperm progressive motility
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• CASA analysis showed a significant reduction in cauda epididymal sperm motility relative to heterozygous control males
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