Interaction of granule, Purkinje and inferior olivary neurons in lurcher chimaeric mice. I. Qualitative studies.

Heterozygous lurcher (+/Lc) mutant mice lose 100% of their Purkinje cells (PCs), 90% of their granule cells, and 75% of their inferior olivary neurons. In order to determine the primary site of Lc gene action, lurcher in equilibrium wild-type aggregation chimaeras were produced. The cerebella of the three chimaeras examined were intermediate or normal in size compared to +/Lc and wild-type cerebella. The PCs were reduced in number. Using the beta-glucuronidase locus (Gus) as a cell marker, all of the PCs present were identified as having descended from the wild-type embryo. It appears that all of the +/Lc PCs degenerated. Hence, the Lc gene acts directly on PCs to cause their degeneration. The inferior olivary nuclei of the chimaeras seemed to have fewer neurons than wild-type but more than +/Lc animals. As revealed by beta-glucuronidase histochemistry, both +/+ and +/Lc cells were present, and the ratio of genotypes was similar to the ratio seen in other regions of the brain. The evidence suggests that the death of olivary neurons in lurcher is secondary to another defect, probably the loss of PCs. Beta-glucuronidase is not an accurate cell marker for granule cells, and so no conclusion concerning the action of the Lc gene on granule cells could be made with these chimaeras.