mortality/aging
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• no mice survive beyond 3 months of age
|
|
|
• the majority of pups fail to survive to weaning
• median survival is 18 days
|
nervous system
|
N |
• brain weight is not significantly decreased and the major anatomical areas of the forebrain are not significantly different from controls
|
|
|
• significantly smaller than control littermates
• however, the posterior lobe is similar in size to that in controls
|
|
|
• 3-fold reduction in proliferating cells in the anterior lobe of the pituitary gland
• no change in proliferation in the posterior lobe
|
|
|
• increases in the numbers of Olig2+ glial and BLBP+ neuroglial progenitors are seen throughout the brain
• expression analysis indicates abnormalities in development and differentiation of neocortical neurons
|
|
|
• at 1 week of age, an increase in proliferating cells is seen in the CA2/3 region
• however, when normalized to the number of progenitor cellsno increase in the percentage of proliferating cells is detected
|
|
|
• decrease in the distance between the corpus callosum and the brain surface in the secondary somatosensory cortex indicating a reduction in cortex thickness
• pre- and post-natal treatment with Rolipram restores normal somatosensory cortical thickness
|
|
|
• increase in the number of NG2+ glial cells in the brain including the somatosensory cortex
|
|
|
• increase in the number of GFAP+ astrocytes in the brain
• gene-dose dependent increase in the number of astrocytes in the CA1 region of the hippocampus
|
|
|
• increase in the number of APC+ oligodendroglial cells in the brain including the fimbria
|
|
|
• apical dendrites of layer II/III pyramidal neurons in the somatosensory cortex are shorter compared to littermate controls
• pre- and post-natal treatment with Rolipram partially restores neurite length
|
|
|
• decrease in intracellular cAMP levels in the brain
|
|
|
• increase in proliferation at E13.5 and to a lesser extent at E17.5 primarily in neuroglial progenitor cells
|
|
|
• significant reduction in growth hormone and prolactin mRNA levels
|
|
|
• 50% reduction in cAMP levels in hypothalamic homogenates
|
growth/size/body
|
|
• greater than 60% reduction in body weight compared to controls by 3 weeks of age
(J:138868)
• weigh about 30% of the weight of control littermates at 2 - 3 months of age
(J:138868)
• Rolipram treatment increases body weight but mice are still smaller than controls
(J:138868)
• at P18, weight is less than 50% that of control littermates
(J:139866)
|
|
|
• severe growth retardation develops during the first week after birth
(J:138868)
• develop progressive growth retardation from P3
(J:139866)
• all major organ systems, except the central nervous system, display growth retardation at P18
(J:139866)
|
endocrine/exocrine glands
|
|
• significantly smaller than control littermates
• however, the posterior lobe is similar in size to that in controls
|
|
|
• 3-fold reduction in proliferating cells in the anterior lobe of the pituitary gland
• no change in proliferation in the posterior lobe
|
|
|
• significant reduction in growth hormone and prolactin mRNA levels
|
homeostasis/metabolism
behavior/neurological
|
|
• extreme sensitivity to handling
|
|
|
• limited range of movement of the hindlimbs
|
cellular
|
|
• increase in proliferation at E13.5 and to a lesser extent at E17.5 primarily in neuroglial progenitor cells
|
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