Sensorimotor disintegration and neurocognitive dysfunction reflect early manifestations of neuropathology in fucosidosis mice
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1
KU Leuven, Belgium
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2
University of Bielefeld, Germany
Fucosidosis is a lysosomal storage disorder caused by lysosomal α-L-fucosidase deficiency. Insufficient α-L-fucosidase activity triggers accumulation of undegraded, fucosylated glycoproteins and glycolipids in various tissues. The central nervous system is prominently affected, leading to neurological deterioration. The human phenotype is heterogeneous, but progressive motor and cognitive impairments constitute the most characteristic symptoms. Recently, Fuca1-deficient mice were generated by gene targeting techniques, constituting a novel animal model for human fucosidosis. These mice display widespread lysosomal storage pathology, accumulation of secondary storage material and neuroinflammation throughout the brain, as well as progressive loss of Purkinje cells. Fuca1-deficient mice and control littermates were subjected to a battery of tests detailing different aspects of motor, emotional and cognitive function. At the age of 3 months, we observed reduced locomotor activity, weaker grip strength, sensorimotor disintegration as well as impaired spatial learning and fear memory. The behavioral phenotype further deteriorates in parallel to their progressive neuropathology. When mice reach the age of 7 months, they show obvious and severely impaired motor coordination and a further decrease in exploratory locomotion. The murine phenotype accurately reflects neuropathological and behavioral hallmarks of human fucosidosis. Fuca1-deficient mice therefore represent a practical and promising model which can be applied for pathogenetic and therapeutic studies.
Keywords:
Lysosomal Storage Diseases,
Fucosidosis,
mouse model,
Behavior, Animal,
Motor function,
Cognitive Function
Conference:
12th National Congress of the Belgian Society for Neuroscience, Gent, Belgium, 22 May - 22 May, 2017.
Presentation Type:
Poster Presentation
Topic:
Disorders of the Nervous System
Citation:
Stroobants
S,
Wolf
H,
Callaerts-Vegh
Z,
Dierks
T,
Lübke
T and
D'Hooge
R
(2019). Sensorimotor disintegration and neurocognitive dysfunction reflect early manifestations of neuropathology in fucosidosis mice.
Front. Neurosci.
Conference Abstract:
12th National Congress of the Belgian Society for Neuroscience.
doi: 10.3389/conf.fnins.2017.94.00017
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Received:
02 May 2017;
Published Online:
25 Jan 2019.
*
Correspondence:
Dr. Stijn Stroobants, KU Leuven, Leuven, Belgium, stijn.stroobants@ppw.kuleuven.be