mortality/aging
• approximately half of homozygotes are embryonic lethal or die at birth
|
• approximately half of homozygotes are embryonic lethal or die at birth
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growth/size/body
• homozygotes are about 30% smaller than wild-type at P10
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• at P10, homozygotes show a 30-40% reduction in mean weight, with a further weight reduction over the next 10 days
|
• homozygotes do not grow at a normal rate 20 days after birth
|
behavior/neurological
• homozygotes at P8-P10 show severe motor abnormalities, such as decreased spontaneous activity and sudden irregular and discoordinated movements
• by P14-P20, homozygotes are nearly unable to perform activities
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• homozygotes are delayed in their ability to right themselves when placed on their backs or in midair
• homozygotes show a difference from wild-type in the midair-righting assay
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bradykinesia
(
J:132813
)
• decrease in spontaneous activity at P8-P10
|
• at P10, mutant pups show severe impairment of ultrasonic vocalization when separated from mothers, producing only a few click-like vocalizations
• at P14-P20, do not produce any ultrasonic vocalization because of the severe loss of activity
|
nervous system
• development of folia of the cerebellum is immature with less folia that are incompletely folded
|
• calbindin-positive Purkinje cells are aligned in a continuous row but are sparsely localized in the folia
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• dendritic shafts of Purkinje cells are thin, with less elaborated calbindin-positive dendritic arbors and reduced synaptophysin reactivity
• dendrites remain at an immature level at P19
|