mortality/aging
• although heterozygous crosses result in normal Mendelian ratios at birth, 40% of homozygotes are lost before 3 weeks of age
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growth/size/body
• mice show a significantly reduced body weight at P1
• at 14 weeks of age, adult mice show a ~60% reduction in body weight relative to wild-type controls
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• mice show a significantly reduced body size at P1 and remain smaller throughout their entire life span
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craniofacial
• adult male mice show a 15% reduction in skull height
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• adult male mice show an allometric reduction in skull length
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• adult male mice show a 15% reduction in skull width
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• adult mice show only a 15% reduction in cranial size relative to the 60% reduction in total body weight
• however, no specific effect on craniofacial development is observed
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reproductive system
• adult males show a 10-fold reduction in total epididymal sperm count relative to wild-type controls
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• >40% of cauda epididymal sperm show morphologic abnormalities, including abnormal sperm head shapes and flagella wrapping
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• sperm flagella wrapping is observed
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• abnormal sperm head shapes are observed
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• TUNEL staining showed increased sperm DNA damage associated with cell death
• however, sperm chromatin condensation appears normal, as shown by chromomycin A3 staining
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• at 14 weeks of age, males show a significantly shorter anal-genital distance (AGD) than wild-type males, even when AGD is corrected for differences in total body length
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• at 14 weeks of age, seminal vesicle weight-to-body weight ratio is ~90% lower than in wild-type males
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• at 14 weeks of age, testis weight-to-body weight ratio is significantly lower than in wild-type males
• however, seminiferous tubule diameters are not altered, and seminiferous epithelium shows complete spermatogenesis
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• 70% of males show an externalized/prolapsed penis by the age of 3 weeks
• 3 of 7 males with penile prolapse are still able to produce copulatory plugs
• no cryptorchidism is observed
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• at 14 weeks of age, epididymis weight-to-body weight ratio is significantly lower than in wild-type males
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• female mice are sterile
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• male mice are sterile
• however, mating behavior is normal
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behavior/neurological
• males exhibit a significantly lower score in a marble burying test than wild-type males
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• in a 30-min open-field test, both sexes spend significantly less time than wild-type controls in exploratory behavior such as rearing up on the hind paws and sniffing
• however, no differences are observed in the time and frequencies spent in the center and in thigmotaxis
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• in a 30-min open-field test, both sexes exhibit a significant increase in the time spent grooming their face and body
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• in a 30-min open-field test, both sexes show a significant reduction in the time spent rearing up on the hind paws
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• during a 30-min open field test, males - but not females - show significantly decreased velocity and total distance traveled relative to wild-type males
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• males exhibit a significantly lower score in nest building behavior than wild-type males
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cellular
• adult males show a 10-fold reduction in total epididymal sperm count relative to wild-type controls
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• >40% of cauda epididymal sperm show morphologic abnormalities, including abnormal sperm head shapes and flagella wrapping
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• sperm flagella wrapping is observed
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• abnormal sperm head shapes are observed
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• TUNEL staining showed increased sperm DNA damage associated with cell death
• however, sperm chromatin condensation appears normal, as shown by chromomycin A3 staining
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nervous system
• adult mice have a disproportionately larger brain relative to the rest of the body
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• at 14 weeks of age, brain weight shows a ~2-fold increase relative to body weight
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skeleton
• adult male mice show a 15% reduction in skull height
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• adult male mice show an allometric reduction in skull length
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• adult male mice show a 15% reduction in skull width
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• adult mice show only a 15% reduction in cranial size relative to the 60% reduction in total body weight
• however, no specific effect on craniofacial development is observed
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digestive/alimentary system
• at 14 weeks of age, males show a significantly shorter anal-genital distance (AGD) than wild-type males, even when AGD is corrected for differences in total body length
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endocrine/exocrine glands
• at 14 weeks of age, seminal vesicle weight-to-body weight ratio is ~90% lower than in wild-type males
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• at 14 weeks of age, testis weight-to-body weight ratio is significantly lower than in wild-type males
• however, seminiferous tubule diameters are not altered, and seminiferous epithelium shows complete spermatogenesis
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renal/urinary system
• 70% of males show an externalized/prolapsed penis by the age of 3 weeks
• 3 of 7 males with penile prolapse are still able to produce copulatory plugs
• no cryptorchidism is observed
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