Analysis Tools
mortality/aging
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• slightly fewer than expected homozygotes are found at birth (about 20.5% versus 25% expected) and about 60% die shortly after or within a few days of birth
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• about 60% die shortly after or within a few days of birth while the remaining 40% survive up to several weeks
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• at P15 homozygotes show signs of premature aging including, graying hair, balding, reduced fat deposition, unstable gait, cachexia, and kyphosis
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respiratory system
atelectasis
(
J:107145
)
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• many newborn homozygotes display diffuse alveolar atelectasis
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• many newborn homozygotes display lack of aeration of the smaller airways suggesting respiratory failure; however, expression of surfactants is similar to wild-type mice
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homeostasis/metabolism
hypoglycemia
(
J:107145
)
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• at P0 and P15 serum glucose levels are 52% and 50% less than wild-type mice, despite the presence of milk in homozygotes' stomachs
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skeleton
short femur
(
J:107145
)
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• short femur with reduced bone mineral density and smaller epiphysis
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• cortical and trabecular bone volume are decreased
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short tibia
(
J:107145
)
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• short tibia with reduced bone mineral density and smaller epiphysis
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• smaller femur and tibia epiphyses
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• cortical and trabecular bone volume are decreased in thoracic vertebral bodies
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osteoporosis
(
J:107145
)
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• delayed bone development
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• mostly calcified cartilage rather than trabecular bone is present at P15
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immune system
small thymus
(
J:107145
)
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• by 2 weeks of age the thymus is moderately smaller
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• by 2 weeks of age severe lymphoid depletion is seen particularly in the cortex
• at P14 thymus cell proliferation is significantly decreased compared to wild-type mice
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cellular
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• by passage 10 an increased proportion of homozygous MEFs have an abnormally high DNA content and increased chromosomal number; however no significant difference in DNA content or chromosome number is seen in the thymus or bone marrow
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• consistent with early senescence phenotype
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• MEFs display early onset senescence and decreased proliferative capacity after passage 6; however, no defect in passage through the the cell cycle is detected
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renal/urinary system
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• epithelial attenuation and accumulation of eosinophilic intracytoplasmic inclusions are seen at 2 weeks of age
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small kidney
(
J:107145
)
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• by 2 weeks of age the kidneys are slightly smaller
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• tubular degeneration is seen at 2 weeks of age
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• at 2 weeks of age
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growth/size/body
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• a decrease in homozygote body weight compared to wild-type mice is first detected at E12.5 and this difference is increased at E15.5 and P0
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• at P0 homozygotes weigh 25% less than wild-type mice
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• by 2 weeks of age homozygotes weigh 70% less than wild-type mice
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• reduction in homozygote body weight is increased at E15.5
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behavior/neurological
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• unstable gait
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adipose tissue
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• by P14 nearly complete loss of the subcutaneous adipose tissue is seen
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pigmentation
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• graying is seen by P15
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limbs/digits/tail
short femur
(
J:107145
)
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• short femur with reduced bone mineral density and smaller epiphysis
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• cortical and trabecular bone volume are decreased
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short tibia
(
J:107145
)
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• short tibia with reduced bone mineral density and smaller epiphysis
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embryo
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• a decrease in homozygote body weight compared to wild-type mice is first detected at E12.5 and this difference is increased at E15.5 and P0
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hematopoietic system
small thymus
(
J:107145
)
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• by 2 weeks of age the thymus is moderately smaller
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• by 2 weeks of age severe lymphoid depletion is seen particularly in the cortex
• at P14 thymus cell proliferation is significantly decreased compared to wild-type mice
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integument
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• by P14 nearly complete loss of the subcutaneous adipose tissue is seen
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• graying is seen by P15
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• hyperkeratosis of the epidermis is seen by P14
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endocrine/exocrine glands
small thymus
(
J:107145
)
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• by 2 weeks of age the thymus is moderately smaller
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• by 2 weeks of age severe lymphoid depletion is seen particularly in the cortex
• at P14 thymus cell proliferation is significantly decreased compared to wild-type mice
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