Purkinje cell loss in the cerebellum of ataxic mutant mouse, dilute-lethal: A fractionator study

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ABSTRACT  This study estimated total number of Purkinje cells in the cerebellum of an ataxic mutant mouse, dilute-lethal (DL), with reference to severe ataxic symptoms of this mutant. On postnatal day (PD) 21, the cerebellar weight is significantly lower in DL than in non-ataxic littermates (control mice). Total number of Purkinje cells is also significantly lower in DL than in the controls; approximately 25% less in DL than in the controls. Furthermore, we performed in situ nick end labeling (TUNEL) -staining in the cerebellum of DL during prenatal and postnatal periods in order to examine the cause of the reduced Purkinje cell number. For analyzes of the mutant fetuses, it is necessary to identify the homozygous mutant. We succeeded in identifying the homozygous DL fetuses from the control fetuses (wild-type or heterozygous fetuses) by the hair color of the grafted skin pieces on nude mice. The histological features of the cerebellar primordium did not differ between the DL and controls on embryonic and postnatal ages examined. In DL, a significantly greater number of TUNEL-positive Purkinje cells was detected on embryonic day (ED) 12, but not throughout ED 14 to PD 21. The results suggest that the Purkinje cell loss in the DL cerebellum is attributed to increased apoptotic cell death of the progenitors. This may be involved in the development of severe ataxic symptoms of DL.

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