Analysis Tools
behavior/neurological
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• adult mice show normal behavior in the Barnes maze and contextual fear conditioning indicating normal spatial learning and memory and associative memory and no alternation in basic motor functions, pain response, social preference, compulsive and impulsive behaviors, or competitive dominant behaviors
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• in the IntelliCage, the discrimination error rate during reversal place learning is lower than in wild-type mice, indicating that mutant mice exhibit increased memory flexibility and better adaptation to new rules
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• in the light-dark box and open-field test, mice show reduced level of anxiety compared with wild-type mice
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nervous system
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• neocortex is expanded at E18.5, with increases in the lateral cortical perimeter and radial thickness, but not ventricle length; increases are most pronounced in the rostral part of the brain
• neocortex expansion persists into adulthood, with increases in width and area at P56 and neocortex showing increased numbers of Satb2+ and Brn2+ upper-layer neurons but not Ctip2+ deep-layer neurons
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• approximate 50% increase in mitotic basal progenitors in the neocortex at E14.5; both mitotic basal radial glia and mitotic basal intermediate progenitors are increased
• however, no change in mitotic apical progenitors in the neocortex is seen
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• thickness of the intermediate zone is increased at E18.5
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• thickness of the cortical plate is increased at E18.5 due to increased numbers of Tbr1+, Ctip2+ and Satb2+ neurons
• increase in cortical plate thickness persists into adulthood, and is due to a specific thickening of the upper cortical layers (layers II + III)
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• substantial increase in the abundance of Pax6+ and Tbr2- and Pax6+ and Tbr2+ basal progenitors, two minor basal progenitor subpopulations, in the subventricular zone (SVZ) plus intermediate zone at E14.5
• however, no change in Pax6+ and Tbr2- apical progenitors in the ventricular zone nor in Pax6+ Tbr2+ newborn basal progenitors in the ventricular zone are seen
• the increase in basal progenitor levels in the neocortical SVZ, results from basal progenitors in the SVZ undergoing self-amplification and not from an increased generation of basal progenitors from apical progenitors in the ventricular zone followed by migration of the newborn basal progenitors to the subventricular zone
• levels of basal mitoses and Tbr2+ cells in the subventricular zone is increased in the neocortex at E12.5, however, the levels of apical mitoses and Tbr2+ cells in the ventricular zone are not different, indicating that the increase in basal progenitor levels is due to increased basal progenitor self-renewal at an even earlier developmental stage
• however, apoptosis levels in the SVZ at E14.5 are not different from wild-type levels
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• increase in cortical neuron numbers at E18.5 that persists into adulthood
• P56 neocortex shows increased numbers of Satb2+ and Brn2+ upper-layer neurons but not Ctip2+ deep-layer neurons
• however, apical and basal dendrite branching, total dendrite branching, dendrite length, dendritic spine number, and spine morphology are unchanged in adult neocortex and cortical fodling is not seen in embryonic or adult stages
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