Analysis Tools
mortality/aging
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• pups born to homozygous mutant mothers died within 24 hrs after birth unless cross-fostered to a wild-type foster mother
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reproductive system
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• at 14.5 days gestation (GD 14.5), mutant mammary glands displayed slightly less glandular tissue than wild-type glands, although the ducts appeared somewhat dilated
• by GD 18.5, mutant mammary glands contained less glandular tissue and more fat while ducts appeared grossly dilated and alveolar tissue was sparse relative to wild-type mice
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• at 3 months of age, the degree of sperm maturation in testes of sexually mature mutants males was similar to that of immature wild-type males at 1 month of age
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• at 3 months of age, mutant epididymides contained less mature sperm than wild-type epididymides
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• whereas the weight of the wild-type male reproductive tract increased 148.6% from 1 month to adulthood representing 3.37% of total body weight, that of mutant males only increased by 87.9% reaching 2.33% of total body weight
• a difference of 31% in the weight ratio of male reproductive tract to body weight between wild-type and mutant mice was observed
• at 1 week and 3 months of age, mutant testis and epididymis tubules and prostate ducts displayed increased collagen deposition associated with more densely packed tubules than those found in wild-type mice
• differences in extracellular matrix correlated with an increased rate of cell apoptosis, as shown by increased Bax (testis, epididymis, and prostate) and caspase-9 (testis) antibody staining at both 1 and 3 months of age
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• by ~6 months of age, mutant prostate glands contained 40% more collagen wild-type prostate tissues
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• mutant prostate glands failed to undergo an age-related increase in growth, as indicated by a decrease in glandular epithelial growth and increased interstitial collagen relative to wild-type prostate glands
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• mutant prostate glands exhibited a reduced epithelial lining, associated with fewer cells
• decreased epithelium was characterized by an increase in cuboidal (low secretory) cells and reduced tall columnar (increased secretory) cells
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• by ~6 months of age, mutant testes contained 19% more collagen wild-type testes
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• at 1 month of age, mutant seminiferous tubules appeared to contain less immature sperm than wild-type tubules
• by 3 months of age, mutant seminiferous tubules were more compact but contained decreased mature sperm, suggesting that maturation of the male reproductive tract was delayed
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small testis
(
J:84575
)
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• starting at 3 months of age, mutant epididymides displayed increased tubule compactness and increased collagen staining relative to wild-type epididymides
• by ~6 months of age, mutant epididymides contained 12% more collagen wild-type epididymides; however, this increase in epididymal collagen was not statistically significant
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• mutant males displayed growth retardation and notable deficiencies in reproductive tract development, esp. in the growth of the prostate
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• 6 of 8 female homozygotes delivered their young in 2.0 0.3 hrs versus 1.7 0.3 hrs in wild-type mice
• the remaining (2 of 8) female homozygotes were unable to deliver normally: one had a protracted labor lasting for 15 hrs, and the other had to be sacrificed because she was in obvious distress having given birth to 2 dead pups ~12 hrs earlier while 10 additional pups (fresh dead) were found in the uterus postmortem
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• mutant males were initially able to impregnate wild-type females at the same frequency as wild-type males; however, as mutant males aged (>4 months of age), the number of days taken by their female wild-type breeding partners to give birth to pups increased with each litter relative to that produced by wild-type pairs
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endocrine/exocrine glands
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• at 2 days after delivery, mutant mammary gland alveoli were in the early stage of involution compared with the cubical secretary cells observed in wild-type controls
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• at 2 days after delivery, mutant alveoli were often smaller and lined by flattened cells with heterochromatic nuclei compared with the cubical cells and euchromatic nuclei observed in normally lactating glands from wild-type mothers
• however, milk secretion was observed in the alveoli and ducts of both wild-type and homozygous mutant mothers
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• at 14.5 days gestation (GD 14.5), mutant mammary glands displayed slightly less glandular tissue than wild-type glands, although the ducts appeared somewhat dilated
• by GD 18.5, mutant mammary glands contained less glandular tissue and more fat while ducts appeared grossly dilated and alveolar tissue was sparse relative to wild-type mice
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• at GD 18.5, mammary gland ducts of homozygous mutant mothers were grossly dilated relative to those of wild-type mothers
• at 2 days after delivery, mutant ducts appeared even more dilated than at GD18.5, and were abnormally lined by squamous epithelial cells instead of the more cubical cells lining the ducts of wild-type mice
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• at 2 days after delivery, the lactating nipples of homozygous mutant mothers retained the histologic appearance of the virgin state, were significantly shorter than wild-type nipples, and unable to support suckling
• however, homozygous mutant mothers did display nursing behavior and pups actively searched for the nipples
• homozygous mutant mothers failed to exhibit thickening of the skin epithelium and loosening of the underlying connective tissue stroma which are typical changes of the wild-type lactating mammary nipple
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• at 2 days after delivery, mutant lactating nipples were significantly shorter than wild-type nipples
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• by ~6 months of age, mutant prostate glands contained 40% more collagen wild-type prostate tissues
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• mutant prostate glands failed to undergo an age-related increase in growth, as indicated by a decrease in glandular epithelial growth and increased interstitial collagen relative to wild-type prostate glands
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• mutant prostate glands exhibited a reduced epithelial lining, associated with fewer cells
• decreased epithelium was characterized by an increase in cuboidal (low secretory) cells and reduced tall columnar (increased secretory) cells
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• by ~6 months of age, mutant testes contained 19% more collagen wild-type testes
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• at 1 month of age, mutant seminiferous tubules appeared to contain less immature sperm than wild-type tubules
• by 3 months of age, mutant seminiferous tubules were more compact but contained decreased mature sperm, suggesting that maturation of the male reproductive tract was delayed
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small testis
(
J:84575
)
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behavior/neurological
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• all newborn or 2-day-old wild-type pups fostered to homozygous mutant mothers failed to suckle, and pups died within 24 hrs with no milk in their stomachs
• in contrast, 26 of 40 homozygous mutant pups fostered to wild-type mothers survived and grew to maturity
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• pups born to homozygous mutant mothers were unable to suckle or stimulate milk let down and died within 24 hrs of birth
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skeleton
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• at full term (GD 18.5), the pubic symphysis of pregnant homozygotes was wider than that of virgin homozygotes (1.65 0.22 mm vs 1.17 0.65 mm, respectively), but significantly narrower that of wild-type mice at full term (5.37 0.64 mm)
• in mutant mice, the interpubic ligament failed to relax and remained short
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homeostasis/metabolism
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• male homozygotes showed no significant differences in hematology, plasma chemistry, or urine analysis relative to wild-type males
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• during late gestation (GD 14.5-18.5), plasma osmolality was significantly higher in homozygous mutant mice than in wild-type controls (316 1 mosmol/kg water vs 306 2 mosmol/kg water, respectively)
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growth/size/body
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• at 2 months of age, both male and female homozygotes were significantly smaller than wild-type controls; however, these size differences were less than those observed at 1 month of age
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• at 1 month (but not at 1 week) of age, mean body weights of both male and female homozygotes were significantly lower than those of aged-matched wild-type controls
• however, differences in body weight became insignificant by 3 months of age
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cellular
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• at 3 months of age, mutant epididymides contained less mature sperm than wild-type epididymides
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• both immature (1 month) and adult (3 month) mutant males exhibited increased Bax (testis, epididymis, and prostate) and caspase-9 (testis) antibody staining relative to wild-type controls
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integument
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• at 2 days after delivery, mutant mammary gland alveoli were in the early stage of involution compared with the cubical secretary cells observed in wild-type controls
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• at 2 days after delivery, mutant alveoli were often smaller and lined by flattened cells with heterochromatic nuclei compared with the cubical cells and euchromatic nuclei observed in normally lactating glands from wild-type mothers
• however, milk secretion was observed in the alveoli and ducts of both wild-type and homozygous mutant mothers
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• at 14.5 days gestation (GD 14.5), mutant mammary glands displayed slightly less glandular tissue than wild-type glands, although the ducts appeared somewhat dilated
• by GD 18.5, mutant mammary glands contained less glandular tissue and more fat while ducts appeared grossly dilated and alveolar tissue was sparse relative to wild-type mice
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• at GD 18.5, mammary gland ducts of homozygous mutant mothers were grossly dilated relative to those of wild-type mothers
• at 2 days after delivery, mutant ducts appeared even more dilated than at GD18.5, and were abnormally lined by squamous epithelial cells instead of the more cubical cells lining the ducts of wild-type mice
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• at 2 days after delivery, the lactating nipples of homozygous mutant mothers retained the histologic appearance of the virgin state, were significantly shorter than wild-type nipples, and unable to support suckling
• however, homozygous mutant mothers did display nursing behavior and pups actively searched for the nipples
• homozygous mutant mothers failed to exhibit thickening of the skin epithelium and loosening of the underlying connective tissue stroma which are typical changes of the wild-type lactating mammary nipple
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• at 2 days after delivery, mutant lactating nipples were significantly shorter than wild-type nipples
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