mortality/aging
• mice survive only until 4-6 weeks of age
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behavior/neurological
• pups display movement disorders characteristic of abnormal cerebellar function
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nervous system
• cerebellar development is more severely affected than in Shhtm2Amc/Shhtm3Amc;Tg(Pcp2-cre)1Amc mice
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• external germinal layer (EGL) is thin at E18.5
• at P5 there is no EGL
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• at P5 cells form a broad densely packed layer at P5; dendrite projections of Purkinje cells are hard to distinguish
• at P14 there is a mixture of Purkinje cell bodies and disorganized cellular projections
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• decreased by 25% at E18.5
• at P5 cell number is reduced by 50%
• in adults, number is reduced by 65%
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• there is no apparent inner germinal layer (IGL) at P5, although at P5 some scattered granule cells can be seen
• in the adult cerebellum, there is no IGL
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• proliferation of granule neuron progenitors is absent in the EGL at E18.5 and P5
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• in the adult cerebellum, molecular layer is absent
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• at E18.5 pups have no lobules
• in the adult cerebellum, there is a loss of rostral lobes
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• at P5, cerebellum is small with some rudimentary lobules
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• disorganization of Bergmann glia is more severe than in Shhtm2Amc/Shhtm3Amc;Tg(Pcp2-cre)1Amc mice post P5
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