Analysis Tools
growth/size/body
|
• at 5 months of age, body weight of males is significantly lower than that of wild-type controls
|
nervous system
|
• in culture, spinal motor neurons (MNs) isolated from E13.5 homozygous mutant embryos show a significant increase in the average axon length and secondary axonal branching relative to wild-type spinal MNs
• interestingly, homozygous spinal MNs have significantly shorter axons than those isolated from heterozygous mutant embryos
• however, hippocampal neurons axonal length is normal
|
|
• homozygotes exhibit disturbed adult neurogenesis in the hippocampus; in the dentate gyrus, the intensity of doublecortin (DCX, a marker for newly differentiated and immature cells) is significantly increased P14, unaltered at P30, and significantly reduced at 4 months of age relative to wild-type controls
• DCX+ neuronal density is significantly reduced at 4 months of age
|
|
• homozygotes exhibit a brain maturation defect during adolescence
• however, no signs of astrogliosis are observed, and cortical layering, cortical thickness, corpus callosum thickness, overall neuronal cell density and neuronal complexity remain normal at 4 month of age
|
|
• at 4 months of age, brain is significantly smaller than normal
|
|
• at 4 months of age, brain weight is significantly lower than that of wild-type controls
• however, no significant change in brain weight is noted at P14 and at P30, and brain-to-body mass ratio is normal at 4 months
|
|
• adult brains show significantly enlarged lateral ventricles
|
|
• adult brains show significantly increased volume of lateral ventricles
|
|
• adult brains show abnormal hippocampal morphology
|
|
• adult brains display a significantly reduced subgranular zone length (SGZ)
• however, SGZ length appears unaffected when normalized to hippocampal volume, and overall cell proliferation as well as neuroblast proliferation in the dentate gyrus are normal
|
|
• adult hippocampi are generally smaller than normal
|
|
• at 4 months of age, the number of DCX+ newborn neurons in the dentate gyrus is significantly decreased
• however, no increase in apoptotic cell death is observed
|
|
• 4-month-old brain lysates show a significant increase in JNK signaling relative to wild-type controls
|
|
• the few DCX+ newborn neurons found in the dentate gyrus at 4 months of age show a tangential orientation rather than integration in the granule cell layer, suggesting a possible migration defect
|
|
• myelin basic protein (MBP) levels are significantly reduced in lysates derived from P30 brains; however, normal MBP levels are detected in lysates from 4-mo-old brains, suggesting a delay in myelination
• however, neurofilament levels are normal suggesting that axon number is unaffected
|
cellular
|
• in culture, spinal motor neurons (MNs) isolated from E13.5 homozygous mutant embryos show a significant increase in the average axon length and secondary axonal branching relative to wild-type spinal MNs
• interestingly, homozygous spinal MNs have significantly shorter axons than those isolated from heterozygous mutant embryos
• however, hippocampal neurons axonal length is normal
|
|
• homozygotes exhibit disturbed adult neurogenesis in the hippocampus; in the dentate gyrus, the intensity of doublecortin (DCX, a marker for newly differentiated and immature cells) is significantly increased P14, unaltered at P30, and significantly reduced at 4 months of age relative to wild-type controls
• DCX+ neuronal density is significantly reduced at 4 months of age
|
|
• the few DCX+ newborn neurons found in the dentate gyrus at 4 months of age show a tangential orientation rather than integration in the granule cell layer, suggesting a possible migration defect
|
reproductive system
|
• homozygotes exhibit a lower fertility rate
|
