Stunted morphologies of cerebellar Purkinje cells in lurcher and staggerer mice are cell-intrinsic effects of the mutant genes

Abstract

Purkinje cells in the neurological mutants lurcher and staggerer exhibit a number of abnormal properties; mutant<==>wild-type chimeras have shown that these properties are direct effects of the mutant gene. What has remained unexplored are the numerous dendritic abnormalities that the two mutant Purkinje cells exhibit. In staggerer, Purkinje cells have rudimentary, unbranched dendrites that lack tertiary branchlet spines. In lurcher, before the Purkinje cells die, their dendrites remain short and underdeveloped. To determine whether or not a system of healthy afferents (or other environmental factors) would alter either of these phenotypes, we examined young lurcher and adult staggerer mouse chimeras using Golgi impregnation. In postnatal day 20 (P20) lurcher chimeras, we found two distinct morphological classes of Purkinje cells. One, inferred to be wild type, had a dendritic structure similar to normal Purkinje cells in age-matched controls. The other consisted of cells with small somata, reduced dendritic arbors, and multiple dendritic processes, making them indistinguishable from Purkinje cells in P20 lurcher mutants. We also examined mature staggerer chimeras. We found no evidence that the stunted morphology of staggerer Purkinje cells is rescued in mosaic animals but observed numerous examples of medium to large neurons resembling atrophic Purkinje cells of staggerer mutants. These results suggest that the dendritic abnormalities described in both mutants reflect cell autonomous, developmental genetic blocks in the cytological maturation of the cerebellar Purkinje cell. The implication is that the action of the wild-type alleles at these two loci are required to execute a normal program of dendritic development.