Acid Ceramidase Deficiency in Mice Results in a Broad Range of Central Nervous System Abnormalities
The result's identifiers
Result code in IS VaVaI
<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00216208%3A11110%2F17%3A10362249" target="_blank" >RIV/00216208:11110/17:10362249 - isvavai.cz</a>
Alternative codes found
RIV/00064165:_____/17:10362249
Result on the web
<a href="http://dx.doi.org/10.1016/j.ajpath.2016.12.005" target="_blank" >http://dx.doi.org/10.1016/j.ajpath.2016.12.005</a>
DOI - Digital Object Identifier
<a href="http://dx.doi.org/10.1016/j.ajpath.2016.12.005" target="_blank" >10.1016/j.ajpath.2016.12.005</a>
Alternative languages
Result language
angličtina
Original language name
Acid Ceramidase Deficiency in Mice Results in a Broad Range of Central Nervous System Abnormalities
Original language description
Farber disease is a rare autosomal recessive disorder caused by acid ceramidase deficiency that usually presents as early-onset progressive visceral and neurologic disease. To understand the neurologic abnormality, we investigated behavioral, biochemical, and cellular abnormalities in the central nervous system of Asah1(P361R/P361R) mice, which serve as a model of Farber disease. Behaviorally, the mutant mice had reduced voluntary locomotion and exploration, increased thigmotaxis, abnormal spectra of basic behavioral activities, impaired muscle grip strength, and defects in motor coordination. A few mutant mice developed hydrocephalus. Mass spectrometry revealed elevations of ceramides, hydroxy-ceramides, dihydroceramides, sphingosine, dihexosylceramides, and monosialodihexosylganglioside in the brain. The highest accumulation was in hydroxy-ceramides. Storage compound distribution was analyzed by mass spectrometry imaging and morphologic analyses and revealed involvement of a wide range of central nervous system cell types (eg, neurons, endothelial cells, and choroid plexus cells), most notably microglia and/or macrophages. Coalescing and mostly perivascular granuloma-like accumulations of storage-laden CD68(+) microglia and/or macrophages were seen as early as 3 weeks of age and located preferentially in white matter, periventricular zones, and meninges. Neurodegeneration was also evident in specific cerebral areas in late disease. Overall, our central nervous system studies in Asah1(P361R/P361R) mice substantially extend the understanding of human Farber disease and suggest that this model can be used to advance therapeutic approaches for this currently untreatable disorder.
Czech name
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Czech description
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Classification
Type
J<sub>imp</sub> - Article in a specialist periodical, which is included in the Web of Science database
CEP classification
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OECD FORD branch
30109 - Pathology
Result continuities
Project
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Continuities
I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace
Others
Publication year
2017
Confidentiality
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů
Data specific for result type
Name of the periodical
American Journal of Pathology
ISSN
0002-9440
e-ISSN
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Volume of the periodical
187
Issue of the periodical within the volume
4
Country of publishing house
US - UNITED STATES
Number of pages
20
Pages from-to
864-883
UT code for WoS article
000398247600016
EID of the result in the Scopus database
2-s2.0-85016006315