Purkinje cell degeneration (pcd) was first identified in a spontaneous mouse mutant showing cerebellar ataxia. In addition to cerebellar Purkinje cells (PCs), retinal photoreceptors, mitral cells in the olfactory bulb, and a discrete subpopulation of thalamic neurons also degenerate in the mutant brains. The gene responsible for the pcd mutant is Nna1, also known as ATP/GTP binding protein 1 or cytosolic carboxypeptidase-like 1, which encodes a zinc carboxypeptidase protein. To investigate pathogenesis of the pcd mutation in detail, we generated a conditional Nna1 allele targeting the carboxypeptidase domain at C-terminus. After Cre recombination and heterozygous crossing, we generated Nna1 knockout (KO) mice and found that the Nna1 KO mice began to show cerebellar ataxia at postnatal day 20 (P20). Most PCs degenerated until 4-week-old, except lobule X. Activated microglia and astrocytes were also observed in the Nna1 KO cerebellum. In the mutant brain, the Nna1 mRNA level was dramatically reduced, suggesting that nonsense-mediated mRNA decay occurs in it. Since the Nna1 protein acts as a de-glutamatase on the C-terminus of α-tubulin and β-tubulin, increased polyglutamylated tubulin was detected in the Nna1 KO cerebellum. In addition, the endoplasmic reticulum stress marker, C/EBP homologous protein (CHOP), was up-regulated in the mutant PCs. We report the generation of a functional Nna1 conditional allele and possible mechanisms of PC death in the Nna1 KO in the cerebellum. OPEN PRACTICES: This article has received a badge for *Open Materials* because it provided all relevant information to reproduce the study in the manuscript. The complete Open Science Disclosure form for this article can be found at the end of the article. More information about the Open Practices badges can be found at https://cos.io/our-services/open-science-badges/.
Pubmed ID: 30225910 RIS Download
Publication data is provided by the National Library of Medicine ® and PubMed ®. Data is retrieved from PubMed ® on a weekly schedule. For terms and conditions see the National Library of Medicine Terms and Conditions.
This monoclonal targets alpha-Tubulin (DM1A) Mouse mAb
View all literature mentionsThis polyclonal targets GFAP
View all literature mentionsThis monoclonal targets Casp3
View all literature mentionsThis polyclonal targets p62
View all literature mentionsThis polyclonal targets Iba1
View all literature mentionsThis polyclonal targets mouse VGluT2, 559-582 aa (BC038375)
View all literature mentionsThis monoclonal targets Tubulin Polyglutamylated antibody produced in mouse
View all literature mentionsThis monoclonal targets Calbindin D-28k
View all literature mentionsThis recombinant monoclonal targets CD11b
View all literature mentionsThis polyclonal secondary targets IgG
View all literature mentionsThis monoclonal targets Glyceraldehyde-3-PDH (GAPDH)
View all literature mentionsThis monoclonal targets LC3A/B
View all literature mentionsThis polyclonal targets IgG
View all literature mentionsThis monoclonal targets actin
View all literature mentionsThis unknown targets Digoxigenin
View all literature mentionsStrain Type: Not Specified This is a legacy resource.
View all literature mentionslaboratory mouse with name Slc:ICR from MGI.
View all literature mentionslaboratory mouse with name Slc:ICR from MGI.
View all literature mentionsThis unknown targets Digoxigenin
View all literature mentionsThis monoclonal targets Casp3
View all literature mentionsThis recombinant monoclonal targets CD11b
View all literature mentionsThis polyclonal targets Iba1
View all literature mentionsThis polyclonal targets GFAP
View all literature mentionsThis polyclonal targets mouse VGluT2, 559-582 aa (BC038375)
View all literature mentionsThis monoclonal targets Glyceraldehyde-3-PDH (GAPDH)
View all literature mentionsThis monoclonal targets actin
View all literature mentionsThis polyclonal targets p62
View all literature mentionsThis monoclonal targets LC3A/B
View all literature mentionsThis monoclonal targets alpha-Tubulin (DM1A) Mouse mAb
View all literature mentionsThis monoclonal targets Tubulin Polyglutamylated antibody produced in mouse
View all literature mentionsStrain Type: Not Specified This is a legacy resource.
View all literature mentionsThis monoclonal targets Calbindin D-28k
View all literature mentionsThis polyclonal targets IgG
View all literature mentionsThis polyclonal secondary targets IgG
View all literature mentions