Analysis Tools
mortality/aging
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• most 5-UF treated mice die unlike similarly treated wild-type mice
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growth/size/body
malocclusion
(
J:178429
)
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• both male and female mice exhibit a significantly smaller size in adulthood
(J:207915)
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• maximum body weight in adulthood is significantly lower than in wild-type mice
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• mice are significantly retarded in gaining body weight both at early and later time points of life
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• in adult mice
(J:178429)
• a delay in postnatal growth is observed by P10
(J:207915)
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hematopoietic system
| N |
• mice do not exhibit anemia or abnormality in hematopoietic organ size
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• mice exhibit fewer long-term repopulating cells (or high proliferative potential colony-forming cells; HPP-CFC) compared with wild-type mice
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• myeloid progenitors are increased compared to in wild-type mice
• granulocyte macrophage progenitors (GMPs) are more than 3 times higher than in wild-type mice
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• the frequencies of short-term and long-term hematopoietic stem cells compared with wild-type mice
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• hematopoietic stem cells exhibit an active state instead of the dormant state observed in wild-type mice
• 5-FU-treated mice fail to exhibit a rebound in peripheral blood cells and most die unlike wild-type mice
|
skeleton
| N |
• at 2-3 months of age, long bone (femurs) show no defects in bone volume, bone formation rate and mineral apposition rate; osteoclast formation from spleen cells is normal
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malocclusion
(
J:178429
)
|
• at 3 months of age, EM analysis showed a decreased average collagen fibril diameter but an increased number of collagen fibrils per area in both tail and Achilles tendons
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• at 2 weeks of age (prior to the appearance of kyphosis), intervertebral spaces appear narrowed both in anterior and posterior regions in the lumbar area
• at 6 weeks of age, lumbar spine shows a progression from relatively normal disc morphology to narrowed intervertebral spaces
• cleared adult skeletons show widening of the intervertebral spaces at the sacrolumbar and sacrococcygeal joints
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• at 6 weeks of age, lumbar spine shows disappearance of the nucleus pulposus
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• at 2 weeks, degeneration of the intervertebral disc is seen at the site of the tail kink, between CA1 and CA2
• at 4 weeks of age, lumbar discs show partial collapse; by 10 weeks, intervertebral spaces are obliterated in the lumbar area
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• at 9 months of age, the sacrum is scoliotic with an unstable and hypertrophic lumbosacral joint and widening of the sacrococcygeal joint
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• although mice appear normal at birth, they exhibit a slight lumbar lordosis by 2 weeks that progresses to severe lordosis together with kyphoscoliosis
• by 8 weeks of age, the spinal deformity is quite severe
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• all mice develop striking thoracic kyphoscoliosis
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• all mice develop striking lumbar lordosis
• a slight lumbar lordosis is observed by 2 weeks of age; this progresses to severe lordosis as mice age
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• by 3 weeks, lordosis is accompanied by thoracic kyphosis
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• in contrast, thoracic spine is normal at 3 months
• at 2 weeks of age, intervertebral spaces appear narrowed both in anterior and posterior regions in the lumbar area
• at 6 weeks, lumbar spine shows a progression to narrowed intervertebral spaces, disappearance of the nucleus pulposus, loss of cartilage, and fusion of vertebrae
• at 7 weeks, lumbar region shows protruding epiphyses, narrowed intervertebral spaces, and rostrally-elongated transverse processes
• at 3 months, lumbar vertebrae, esp. L2 and L3, are dysmorphic: the neural canal is abnormally large, the bone is less dense, and the neural spine is wider and shorter; vertebrae are also slightly smaller and shorter
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• by 9 months of age, articular processes of lumbar vertebrae, including the prezygapophysis, are fused over their dorsolateral regions
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• at 7 weeks, lumbar region shows rostrally-elongated transverse processes
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• at 10 weeks, mice show spontaneous fusion between vertebrae throughout the lumbar, sacral, and caudal regions
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• by 9 months of age, the L3-L6 segment is fused in lordosis: centra are fused with prominent epiphyses, dorsolateral articulations, including the pre- and postzygapophysis processes are fused to their adjacent counterpart, and neural processes are short and fused
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• at P7, EM analysis showed collagen fibers of varying diameter with little consistency in orientation in lumbar intervertebral discs
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• at P10, mice show mild osteopenia in the lumbar region with no defects in the intervertebral discs
• at 4 weeks, marked osteopenia is observed in lumbar vertebrae with narrowing and fusion of some lumbar discs
• by 3 months, vertebral trabecular bone volume is markedly reduced with a decrease in vertebral trabecular thickness, trabecular number, and connectivity density
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• at P6 and P10, upper lumbar vertebrae display a decreased bone volume/total volume ratio
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• at P6 and P10, upper lumbar vertebrae display a decreased trabecular number
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• at P6 and P10, upper lumbar vertebrae display higher trabecular spacing
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• at P6 and P10, upper lumbar vertebrae display reduced connectivity density
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• at 3 months of age, lumbar vertebrae display a decrease in vertebral trabecular thickness
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• cleared adult skeletons show exostosis at the epiphysis/vertebral-disc junction in the lumbar area
• at 2 weeks, degeneration of the intervertebral disc is seen at the site of the tail kink, between CA1 and CA2, with exostosis at the caudal end of CA1
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• at 3 months of age, EM analysis showed a decreased average collagen fibril diameter but an increased number of collagen fibrils per area in sacral ligaments
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• at 2 weeks, focal delay of endochondral ossification of lumbar vertebral growth plates is observed; caudal growth plate is more affected than the cranial growth plate
• however, endochondral bone formation is normal
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• at 3.5 months of age, bio-mechanical testing of femurs showed a decrease in bone strength
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immune system
craniofacial
malocclusion
(
J:178429
)
reproductive system
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• both male and mice show reduced fertility
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limbs/digits/tail
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• mice show a dorsally-positioned (dorsiflexed) tail
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behavior/neurological
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• mice show a slight abduction of the hindlimbs
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muscle
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• at 3 months of age, EM analysis showed a decreased average collagen fibril diameter but an increased number of collagen fibrils per area in both tail and Achilles tendons
|
homeostasis/metabolism
| N |
• serum calcium, phosphorus and osteocalcin levels are normal
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• most 5-UF treated mice die unlike similarly treated wild-type mice
|
neoplasm
