ZFIN ID: ZDB-PUB-110110-15
rnaset2 mutant zebrafish model familial cystic leukoencephalopathy and reveal a role for RNase T2 in degrading ribosomal RNA
Haud, N., Kara, F., Diekmann, S., Henneke, M., Willer, J.R., Hillwig, M.S., Gregg, R.G., Macintosh, G.C., Gärtner, J., Alia, A., and Hurlstone, A.F.
Date: 2011
Source: Proceedings of the National Academy of Sciences of the United States of America   108(3): 1099-1103 (Journal)
Registered Authors: Gregg, Ronald G., Hurlstone, Adam, Willer, Jason
Keywords: none
MeSH Terms:
  • Animals
  • Brain/metabolism
  • Cell Line
  • Cloning, Molecular
  • Fluorescent Antibody Technique
  • Gene Knockdown Techniques
  • Humans
  • In Situ Hybridization
  • Leukoencephalopathies/genetics*
  • Lysosomal Storage Diseases/genetics*
  • Lysosomes/metabolism*
  • Magnetic Resonance Imaging
  • Microscopy, Electron, Transmission
  • Neurons/metabolism
  • Neurons/pathology
  • RNA Stability/genetics
  • RNA Stability/physiology*
  • RNA, Ribosomal/metabolism*
  • Ribonucleases/genetics
  • Ribonucleases/metabolism*
  • Tumor Suppressor Proteins/genetics
  • Tumor Suppressor Proteins/metabolism*
  • Zebrafish/genetics*
PubMed: 21199949 Full text @ Proc. Natl. Acad. Sci. USA
T2-family acidic endoribonucleases are represented in all genomes. A physiological role for RNase T2 has yet to be defined for metazoa. RNASET2 mutation in humans is linked with a leukoencephalopathy that arises in infancy characterized by cortical cysts and multifocal white matter lesions. We now show localization of RNASET2 within lysosomes. Further, we demonstrate that loss of rnaset2 in mutant zebrafish results in accumulation of undigested rRNA within lysosomes within neurons of the brain. Further, by using high field intensity magnetic resonance microimaging, we reveal white matter lesions in these animals comparable to those observed in RNASET2-deficient infants. This correlates with accumulation of Amyloid precursor protein and astrocytes at sites of neurodegeneration. Thus we conclude that familial cystic leukoencephalopathy is a lysosomal storage disorder in which rRNA is the best candidate for the noxious storage material.