Purkinje cell degeneration ( pcd ) Phenotypes Caused by Mutations in the Axotomy-Induced Gene, Nna1

• DOI: 10.1126/science.1068912
• Publication Date: 2002-07-27T09:35:18Z
• Authors: Angeles Fernandez...; Albert R. La Spada; Jason Treadaway; Jason C. Higdon; Belinda S. Harris; Richard L. Sidman; James I. Morgan; Jian Zuo
• Keywords: Male; 0301 basic medicine; Blotting-Northern; Molecular Sequence Data; Gene-Expression; In-Situ-Hybridization; 610; Gene Expression; Carboxypeptidases; Retina; Mice; Mice, Neurologic Mutants; 03 medical and health sciences; Purkinje-Cells; GTP-Binding Proteins; SUPPORT-U-S-GOVT-P-H-S; Testis; 616; Animals; Nerve-Regeneration; Spermatogenesis; SUPPORT-NON-U-S-GOVT; Alleles; Crosses, Genetic; In Situ Hybridization; Neurons; 0303 health sciences; Animal; Mice-Neurologic-Mutants; RNA-Messenger; Brain; Chromosome Mapping; Crosses-Genetic; Axotomy; Blotting, Northern; GTP-Binding-Proteins; Nerve Regeneration; Nerve-Degeneration; Phenotype; Genes; Chromosome-Mapping; Mutation; Nerve Degeneration; Female

The classical recessive mouse mutant, Purkinje cell degeneration ( pcd ), exhibits adult-onset degeneration of cerebellar Purkinje neurons, retinal photoreceptors, olfactory bulb mitral neurons, and selected thalamic neurons, and has defective spermatogenesis. Here we identify Nna1 as the gene mutated in the original pcd and two additional pcd alleles ( pcd 2J and pcd 3J ). Nna1 encodes a putative nuclear protein containing a zinc carboxypeptidase domain initially identified by its induction in spinal motor neurons during axonal regeneration. The present study suggests an unexpected molecular link between neuronal degeneration and regeneration, and its results have potential implications for neurodegenerative diseases and male infertility.