Purkinje cell degeneration (pcd) phenotypes caused by mutations in the axotomy-induced gene, Nna1.
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.
Fernandez-Gonzalez
Angeles
A
Department of Developmental Neurobiology, St. Jude Children's Research Hospital, Memphis, TN 38105, USA.
La Spada
Albert R
AR
Treadaway
Jason
J
Higdon
Jason C
JC
Harris
Belinda S
BS
Sidman
Richard L
RL
Morgan
James I
JI
Zuo
Jian
J
D000483:Alleles; D000818:Animals; D019771:Axotomy; D015152:Blotting, Northern; D001921:Brain / Q000378:metabolism; D002268:Carboxypeptidases; D002874:Chromosome Mapping; D003433:Crosses, Genetic; D005260:Female; D019204:GTP-Binding Proteins / Q000737:chemistry / Q000235:genetics* / Q000502:physiology*; D015870:Gene Expression; D005796:Genes; D017403:In Situ Hybridization; D008297:Male; D051379:Mice; D008818:Mice, Neurologic Mutants; D008969:Molecular Sequence Data; D009154:Mutation; D009410:Nerve Degeneration / Q000235:genetics*; D009416:Nerve Regeneration; D009474:Neurons / Q000378:metabolism; D010641:Phenotype; D011689:Purkinje Cells / Q000166:cytology / Q000502:physiology*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D012160:Retina / Q000378:metabolism; D046929:Serine-Type D-Ala-D-Ala Carboxypeptidase; D013091:Spermatogenesis; D013737:Testis / Q000378:metabolism
D012333:RNA, Messenger; D002268:Carboxypeptidases; D046929:Serine-Type D-Ala-D-Ala Carboxypeptidase; C420042:Agtpbp1 protein, mouse; D019204:GTP-Binding Proteins