Purkinje cell degeneration (pcd) phenotypes caused by mutations in the axotomy-induced gene, Nna1

Science. 2002 Mar 8;295(5561):1904-6. doi: 10.1126/science.1068912.

Abstract

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 (pcd2J and pcd3J). 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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Alleles
  • Animals
  • Axotomy*
  • Blotting, Northern
  • Brain / metabolism
  • Carboxypeptidases*
  • Chromosome Mapping
  • Crosses, Genetic
  • Female
  • GTP-Binding Proteins / chemistry
  • GTP-Binding Proteins / genetics*
  • GTP-Binding Proteins / physiology*
  • Gene Expression
  • Genes
  • In Situ Hybridization
  • Male
  • Mice
  • Mice, Neurologic Mutants
  • Molecular Sequence Data
  • Mutation*
  • Nerve Degeneration / genetics*
  • Nerve Regeneration
  • Neurons / metabolism
  • Phenotype
  • Purkinje Cells / cytology
  • Purkinje Cells / physiology*
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Retina / metabolism
  • Serine-Type D-Ala-D-Ala Carboxypeptidase*
  • Spermatogenesis
  • Testis / metabolism

Substances

  • RNA, Messenger
  • Carboxypeptidases
  • Serine-Type D-Ala-D-Ala Carboxypeptidase
  • Agtpbp1 protein, mouse
  • GTP-Binding Proteins

Associated data

  • GENBANK/AE008685
  • GENBANK/AF457126