The zinc-binding domain of Nna1 is required to prevent retinal photoreceptor loss and cerebellar ataxia in Purkinje cell degeneration ( pcd) mice

• Published in: Vision research (Oxford) Vol. 48; no. 19; pp. 1999 - 2005
• Main Authors: Chakrabarti, Lisa, Eng, Jeremiah, Martinez, Refugio A., Jackson, Stephen, Huang, Jing, Possin, Daniel E., Sopher, Bryce L., Spada, Albert R. La
• Format: Journal Article
• Language: English
• Published: Oxford Elsevier Ltd 01.09.2008; Elsevier Science
• Subjects: Amino Acid Sequence; Animals; Biological and medical sciences; Cerebellar Ataxia - genetics; Cerebellar Ataxia - pathology; Cerebellar Ataxia - physiopathology; Eye and associated structures. Visual pathways and centers. Vision; Fundamental and applied biological sciences. Psychology; Genetic rescue; Genotype; GTP-Binding Proteins - genetics; GTP-Binding Proteins - metabolism; GTP-Binding Proteins - physiology; Mice; Mice, Transgenic; Molecular Sequence Data; Polymerase Chain Reaction - methods; Purkinje cell degeneration; Purkinje Cells - pathology; Retinal Degeneration - genetics; Retinal Degeneration - metabolism; Retinal Degeneration - pathology; Retinal Degeneration - physiopathology; Retinal photoreceptor degeneration; Serine-Type D-Ala-D-Ala Carboxypeptidase - genetics; Serine-Type D-Ala-D-Ala Carboxypeptidase - metabolism; Serine-Type D-Ala-D-Ala Carboxypeptidase - physiology; Vertebrates: nervous system and sense organs; Zinc - metabolism; Zinc-dependent carboxypeptidase; Purkinje cell degeneration; Zinc-dependent carboxypeptidase; Retinal photoreceptor degeneration; Genetic rescue; Cerebellar ataxia; Rodentia; Purkinje neuron; Photoreceptor; Retina; Zinc; Retinal photoreceptor degeneration;Zinc-dependent carboxypeptidase;Genetic rescue;Purkinje cell degeneration; Eye; Visual system; Vertebrata; Mammalia; Mouse; Animal; Degeneration
• ISSN: 0042-6989; 1878-5646
• DOI: 10.1016/j.visres.2008.05.026

The Purkinje cell degeneration ( pcd) mouse undergoes retinal photoreceptor degeneration and Purkinje cell loss. Nna1 is postulated to be the causal gene for pcd. We show that a BAC containing the Nna1 gene rescues retinal photoreceptor loss and Purkinje cell degeneration, confirming that Nna1 loss-of-function is responsible for these phenotypes. Mutation of the zinc-binding domain within the transgene destroyed its ability to rescue neuronal loss in pcd 5J homozygous mice. In conclusion, Nna1 is required for survival of retinal photoreceptors and other neuron populations that degenerate in pcd mice. A functional zinc-binding domain is crucial for Nna1 to support neuron survival.