The Purkinje cell degeneration (pcd) mouse: an unexpected molecular link between neuronal degeneration and regeneration

Abstract

The spontaneous autosomal recessive mouse mutation, Purkinje cell degeneration (pcd), was first identified through its ataxic behavior. Since its discovery in the 1970s, the strain has undergone extensive investigation, although another quarter century elapsed until the mutant gene (agtpbp1 a.k.a. Nna1) underlying the pcd phenotype was identified. As Nna1 was initially discovered as a gene induced in motor neurons following axotomy the finding that its loss leads to selective neuronal degeneration points to a novel and unexpected common molecular mechanism contributing to the apparently opposing processes of degeneration and regeneration. The elucidation of this mechanism may of course have significant implications for an array of neurological disorders. Here we will first review the principle features of the pcd phenotype and then discuss the functional implications of more recent findings emanating from the characterization of Nna1, the protein that is lost in pcd. We also provide new data on the genetic dissection of the cell death pathways operative in pcd(3J) mice, proving that granule cell death and Purkinje cell death in these mice have distinct molecular bases. We also provide new information on the structure of mouse Nna1 as well as Nna1 protein levels in pcd(3J) mice.