rnaset2 mutant zebrafish model familial cystic leukoencephalopathy and reveal a role for RNase T2 in degrading ribosomal RNA

• DOI: 10.1073/pnas.1009811107
• Publication Date: 2011-01-04T04:10:13Z
• Authors: Noémie Haud; Firat Kara; Simone Diekmann; Marco Henneke; Jason R. Willer; Melissa S. Hillwig; Ronald G. Gregg; Gustavo C. MacIntosh; Jutta Gärtner; A. Alia; Adam F. L. Hurlstone
• Keywords: Neurons; 0301 basic medicine; RNA Stability; Tumor Suppressor Proteins; Brain; Fluorescent Antibody Technique; Magnetic Resonance Imaging; Cell Line; 3. Good health; Lysosomal Storage Diseases; 03 medical and health sciences; Ribonucleases; Microscopy, Electron, Transmission; Leukoencephalopathies; RNA, Ribosomal; Gene Knockdown Techniques; Animals; Humans; Cloning, Molecular; Lysosomes; In Situ Hybridization; Zebrafish

T2-family acidic endoribonucleases are represented in all genomes. A physiological role for RNase T2 has yet to be defined metazoa. RNASET2 mutation humans is linked with a leukoencephalopathy that arises infancy characterized by cortical cysts and multifocal white matter lesions. We now show localization of within lysosomes. Further, we demonstrate loss rnaset2 mutant zebrafish results accumulation undigested rRNA lysosomes neurons the brain. using high field intensity magnetic resonance microimaging, reveal lesions these animals comparable those observed RNASET2-deficient infants. This correlates Amyloid precursor protein astrocytes at sites neurodegeneration. Thus conclude familial cystic lysosomal storage disorder which best candidate noxious material.