36. Development of Purkinje Cells in the Cerebellum of xpg-Deficient Mice

Xue-Zhi Sun, Yoshi-Nobu Harada, Sentaro Takahashi, Naoko Shiomi and Tadahiro Shiomi

Keywords: cerebellar cortex, Cockayne syndrome, degeneration, immunohistochemistry

A mutant mouse carrying nonfunctional xeroderma pigmentosum group G gene (the mouse counterpart of the human XPG gene) alleles has been generated by using gene-targeting and embryonic stem cell technology. Homozygote animals of this autosomal recessive disease exhibited signs and symptoms, such as postnatal growth retardation, reduced levels of activity, progressive ataxia and premature death, similar to the clinical manifestations of Cockayne syndrome (CS). Histological analysis of the cerebellum revealed multiple pyknotic cells in the Purkinje cell layer of the xpg homozygotes, which had atrophic cell bodies and shrunken nuclei. Further examination by immunohistochemistry for calbindin-D 28k (CaBP) showed that a large number of immunoreactive Purkinje cells were atrophic and their dendritic trees were smaller and shorter than in wild-type littermates. These results indicated a marked degeneration of Purkinje cells in the xpg mutant cerebellum. Study by in situ detection of DNA fragmentation in the cerebellar cortex demonstrated that some TUNEL-positive cells appeared in the granule layer of the mutant mice, but few cell deaths were confirmed in the Purkinje layer. These results suggested Purkinje cell degeneration in the mutant cerebellum was underway, in which many Purkinje cell deaths had not appeared, and the appearance of some abnormal cerebellar symptoms in the xpg-deficient mice was not only due to a marked Purkinje cell degeneration, but also to damage to other cells.