RNaseT2 knockout rats exhibit hippocampal neuropathology and deficits in memory

Disease Models & Mechanisms
Kerstin W SinkeviciusCraig F Ferris

Abstract

RNASET2 deficiency in humans is associated with infant cystic leukoencephalopathy, which causes psychomotor impairment, spasticity and epilepsy. A zebrafish mutant model suggests that loss of RNASET2 function leads to neurodegeneration due to the accumulation of non-degraded RNA in the lysosomes. The goal of this study was to characterize the first rodent model of RNASET2 deficiency. The brains of 3- and 12-month-old RNaseT2 knockout rats were studied using multiple magnetic resonance imaging modalities and behavioral tests. While T1- and T2-weighted images of RNaseT2 knockout rats exhibited no evidence of cystic lesions, the prefrontal cortex and hippocampal complex were enlarged in knockout animals. Diffusion-weighted imaging showed altered anisotropy and putative gray matter changes in the hippocampal complex of the RNaseT2 knockout rats. Immunohistochemistry for glial fibrillary acidic protein (GFAP) showed the presence of hippocampal neuroinflammation. Decreased levels of lysosome-associated membrane protein 2 (LAMP2) and elevated acid phosphatase and β-N-acetylglucosaminidase (NAG) activities indicated that the RNASET2 knockout rats likely had altered lysosomal function and potential defects in autophagy. Object recogniti...Continue Reading

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Citations

May 8, 2021·Frontiers in Genetics·Vanessa ChenouardIgnacio Anegon
May 10, 2021·The Journal of Immunology : Official Journal of the American Association of Immunologists·David A HumeKatharine M Irvine
Jun 24, 2021·International Immunology·Kaiwen LiuKensuke Miyake
Jul 6, 2021·International Immunology·Kensuke MiyakeYusuke Murakami

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Methods Mentioned

BETA
PCR
biopsies
electrophoresis
X-ray

Software Mentioned

Matlab
GraphPad Prism
Unix
ANY
Deformable Registration via Attribute Matching and Mutual Sali...
ImageJ
maze
MedINRIA
MIVA

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