The fine structure of the Purkinje cell and its afferents in lurcher chimeric mice.

Lurcher is an autosomal dominant mutation in the mouse. Heterozygote (+/Lc) animals lose 100% of their cerebellar Purkinje cells during the first postnatal month. Aggregation chimeras made between +/Lc and wild-type embryos have been used to demonstrate that this neuronal cell death is a cell autonomous property of the +/Lc Purkinje cells. In lurcher chimeras, all +/Lc PCs die while wild-type Purkinje cells survive in the numbers expected. Although they are normal in number, previous work from our laboratories has shown that when the genetically wild-type Purkinje cells are present in the mosaic environment of the lurcher chimeric mouse they develop a very unusual morphology. Their dendritic trees are small, and the caliber of their dendrites is increased. This paper examines the fine structure of these unusual cells as well as their afferent fibers. Purkinje cell somas in the lurcher chimera have an increased number of lysosomes and the rough endoplasmic reticulum is improperly configured. In the majority of the Purkinje cell dendrites the organelles are disorganized; it is not certain whether this is a cause or a consequence of the increase in dendritic caliber previously reported. Presynaptic fibers have been examined and, while all classes of expected synapses can be observed, the numbers of synaptic profiles visible in any one thin section are reduced. Climbing fiber terminations on the Purkinje cells were smaller than normal with a greatly diminished number of constituent vesicles. Unexpectedly, we found unusual morphologies among the Bergmann glial fibers and the presence of unusual (or ectopic) astrocytic like glial cells near the pial surface. These changes in turn were accompanied by an increase in the number of glial-like fibers near the pia in some parts of the chimeric cerebellar cortex. The results are discussed in light of our knowledge of other mutant mice, and a hypothesis is put forward to explain some of our results.