TY  - JOUR
AB  - Fucosidosis is a rare lysosomal storage disorder caused by the
inherited deficiency of the lysosomal hydrolase α-L-fucosidase, which
leads to an impaired degradation of fucosylated glycoconjugates.
Here, we report the generation of a fucosidosis mouse model, in
which the gene for lysosomal α-L-fucosidase (Fuca1) was disrupted
by gene targeting. Homozygous knockout mice completely lack
α-L-fucosidase activity in all tested organs leading to highly
elevated amounts of the core-fucosylated glycoasparagine Fuc
(α1,6)-GlcNAc(β1-N)-Asn and, to a lesser extent, other fucosylated
glycoasparagines, which all were also partially excreted in urine.
Lysosomal storage pathology was observed in many visceral organs,
such as in the liver, kidney, spleen and bladder, as well as in the
central nervous system (CNS). On the cellular level, storage was
characterized by membrane-limited cytoplasmic vacuoles primarily
containing water-soluble storage material. In the CNS, cellular
alterations included enlargement of the lysosomal compartment in
various cell types, accumulation of secondary storage material and
neuroinflammation, as well as a progressive loss of Purkinje cells
combined with astrogliosis leading to psychomotor and memory
deficits. Our results demonstrate that this new fucosidosis mouse
model resembles the human disease and thus will help to unravel
underlying pathological processes. Moreover, this model could be
utilized to establish diagnostic and therapeutic strategies for fucosidosis.
DA  - 2016
DO  - 10.1242/dmm.025122
KW  - Fucosidosis
KW  - Neurodegeneration
KW  - Lysosomal storage disorder
LA  - eng
IS  - 9
M2  - 1015
PY  - 2016
SN  - 1754-8403
SP  - 1015-1028
T2  - Disease Models & Mechanisms
TI  - A mouse model for fucosidosis recapitulates storage pathology and neurological features of the milder form of the human disease
UR  - https://nbn-resolving.org/urn:nbn:de:0070-pub-29056164
Y2  - 2024-11-24T18:34:51
ER  -