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 ↔ 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 β-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 β-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. β-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.

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At least 150 olivary neurons were counted for each chimaera. In control Gusb/Gusb sections, the staining of the olivary neurons ranged from heavy to light, but olivary neurons of Gush/Gush animals were always unstained. In the chimaeras, the genotypes of Some neurons were ambiguous due to intercellular enzyme transfer, variability in background staining, etc. The number of ambiguous neurons was less than 5 % of our counts, and so these factors did not prevent us from accurately determining the genotypes of the vast majority of the olivary neurons.

Copyright © 1982 by Company of Biologists
1982
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