Analysis Tools
mortality/aging
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• homozygotes that survive the first day after birth are viable with equivalent longevity to wild-type littermates
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• although present at normal Mendelian ratios from E11.5 to E18.5, the number of homozygotes is significantly reduced at P0, suggesting lethality during or directly after birth
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growth/size/body
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• neonates show reduced body weight relative to wild-type controls
• at 18 months of age, males show a significantly lower body weight than wild-type controls, with a similar trend observed in females
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• males gain significantly less weight than wild-type males from 10 to 40 weeks of age
• however, females show normal weight gain
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• body size is significantly reduced at E15.5
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• body weight is significantly reduced at E18.5 and P0
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• body size is significantly reduced from E15.5 onwards
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respiratory system
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• respiratory rate is significantly reduced at P0
• however, respiratory rate is recovered in neonates that survive the first day after birth and surviving pups reach adulthood
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skeleton
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• shorter skulls at E15.5
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• at E15.5, ossification of the frontal bone of the cranial vault is delayed
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• at E15.5, ossification of the mandible is delayed
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• at E15.5, ossification of the premaxilla is delayed
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• at E18.5, ossification of the proximal and distal phalanges is delayed
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• femur width is significantly reduced at E15.5 and E18.5
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short femur
(
J:277387
)
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• femur length is significantly reduced at E15.5 but not at E18.5
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• at E15.5, the length of the hypertrophic zone in humeral growth plates is increased; the expression area of the hypertrophic marker collagen X and the osteogenic markers osteocalcin and osteopontin is expanded
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• at E15.5, the chondro-osseous junction in humeral growth plates appears disorganized, indicating premature hypertrophy
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• at E15.5, size and ossification of the lumbar vertebrae is reduced
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• limb bud mass cultures from E11.5 embryos show a trend towards increased Alcian Blue staining (proteoglycan synthesis) and significantly increased transcription of chondrogenic markers (aggrecan and Indian hedgehog) relative to wild-type cultures, indicating accelerated in vitro chondrogenic differentiation
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• at E15.5, ossification of the lumbar vertebrae is delayed
• at E18.5, ossification of the proximal and distal phalanges is delayed
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• at E15.5, ossification of the frontal bone of the cranial vault, the premaxilla and the mandible is delayed
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• after 14 days of osteogenic differentiation-inducing treatment, primary MEFs show no von Kossa or Alizarin Red staining, unlike wild-type MEFs; also, no increase in expression of the osteogenic transcription factor osterix and the matrix proteins osteocalcin and bone sialoprotein is observed, indicating impaired in vitro osteogenic differentiation
• dysregulation of FAK/Src-PI3K/AKT signaling in MEFs may contribute to reduced osteogenic differentiation
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adipose tissue
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• mice exhibit a defect in the generation of adipocytes and the accumulation of lipids, indicating reduced adipogenesis
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• after 7 days of adipogenic differentiation-inducing treatment, primary MEFs show poor Oil Red O staining, unlike wild-type MEFs; no subsequent high induction of PPARgamma and C/EBPalpha, or later expression of the adipogenic markers adiponectin and Glut4 is observed, indicating impaired in vitro adipocyte differentiation
• FAK/Src-PI3K/AKT signaling pathway is dysregulated in MEFs; however, no differences in focal adhesion formation or cell adhesion are observed
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• neonates exhibit significantly fewer lipid-filled (perilipin A-positive) subcutaneous adipocytes in the scapular region relative to wild-type controls
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• at 18 months of age, the size of adipocytes in perigonadal WAT is significantly deceased
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• at 18 months of age, perigonadal fat pad weight is significantly decreased in both sexes
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• at 18 months of age, retroperitoneal fat pad weight is significantly decreased in males, with a similar trend observed in females
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cellular
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• in vitro, mesenchymal progenitor cells show enhanced differentiation into chondrocytes, but impaired differentiation into adipocytes and osteoblasts
• impaired adipogenic differentiation in MEFs is rescued by FAK activation while defective adipogenic and osteogenic differentiation are both associated with dysregulated Src and AKT signaling
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• after 7 days of adipogenic differentiation-inducing treatment, primary MEFs show poor Oil Red O staining, unlike wild-type MEFs; no subsequent high induction of PPARgamma and C/EBPalpha, or later expression of the adipogenic markers adiponectin and Glut4 is observed, indicating impaired in vitro adipocyte differentiation
• FAK/Src-PI3K/AKT signaling pathway is dysregulated in MEFs; however, no differences in focal adhesion formation or cell adhesion are observed
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craniofacial
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• shorter skulls at E15.5
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• at E15.5, ossification of the frontal bone of the cranial vault is delayed
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• at E15.5, ossification of the mandible is delayed
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• at E15.5, ossification of the premaxilla is delayed
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limbs/digits/tail
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• at E18.5, ossification of the proximal and distal phalanges is delayed
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• at E15.5, size and ossification of the hind limbs is reduced
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• femur width is significantly reduced at E15.5 and E18.5
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short femur
(
J:277387
)
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• femur length is significantly reduced at E15.5 but not at E18.5
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cardiovascular system
| N |
• neonates exhibit no obvious vascular defects
• retinal angiogenesis and lymphangiogenesis are normal
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neoplasm
