Abnormalities of Purkinje cell arborization in brindled mouse cerebellum. A Golgi study.

The cerebellum of the hemizygous brindled mouse (MObr/y), a murine model of Kinky hair disease (KHD) in human beings, was investigated chronologically using the Golgi technique. In 15-day-old MObr/y, Purkinje cells showed considerable changes in their arborization such as perisomatic dendrite-like processes, numerous spine-like protrusions from somata and stem dendrites, focal swellings of stem and distal dendrites and generally poor development of dendritic trees. These changes closely resembled those of KHD. Similar changes except for the focal swellings of dendrites, could be found in control mice at day eight but never after day 12. In the MObr/y receiving intraperitoneal injections of cupric chloride (CuCl2) on postnatal (PN) days seven and ten, Purkinje cells appeared similar, if not identical, to those of controls at PN day 15. Focal swellings of dendrites transiently reappeared in treated animals after PN day 23 but spontaneously subsided by day 110. These results suggested that normal arborization of Purkinje cells in MObr/y is at least in part due to delayed maturation, which is correctable by cupric chloride (CuCl2) treatment. The "weeping willow" deformity, which characterizes Purkinje cells in KHD in humans were not observed in MObr/y. Because other neuronal populations, which are known to be deficient in KHD, appeared well preserved in the murine mutant, these dendritic deformities may be secondary to the loss of other neurons.