A comprehensive phenotypic characterization of a whole-body Wdr45 knock-out mouse
The result's identifiers
Result code in IS VaVaI
<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F68378050%3A_____%2F21%3A00544058" target="_blank" >RIV/68378050:_____/21:00544058 - isvavai.cz</a>
Result on the web
<a href="https://link.springer.com/article/10.1007%2Fs00335-021-09875-3" target="_blank" >https://link.springer.com/article/10.1007%2Fs00335-021-09875-3</a>
DOI - Digital Object Identifier
<a href="http://dx.doi.org/10.1007/s00335-021-09875-3" target="_blank" >10.1007/s00335-021-09875-3</a>
Alternative languages
Result language
angličtina
Original language name
A comprehensive phenotypic characterization of a whole-body Wdr45 knock-out mouse
Original language description
Pathogenic variants in the WDR45 (OMIM: 300,526) gene on chromosome Xp11 are the genetic cause of a rare neurological disorder characterized by increased iron deposition in the basal ganglia. As WDR45 encodes a beta-propeller scaffold protein with a putative role in autophagy, the disease has been named Beta-Propeller Protein-Associated Neurodegeneration (BPAN). BPAN represents one of the four most common forms of Neurodegeneration with Brain Iron Accumulation (NBIA). In the current study, we generated and characterized a whole-body Wdr45 knock-out (KO) mouse model. The model, developed using TALENs, presents a 20-bp deletion in exon 2 of Wdr45. Homozygous females and hemizygous males are viable, proving that systemic depletion of Wdr45 does not impair viability and male fertility in mice. The in-depth phenotypic characterization of the mouse model revealed neuropathology signs at four months of age, neurodegeneration progressing with ageing, hearing and visual impairment, specific haematological alterations, but no brain iron accumulation. Biochemically, Wdr45 KO mice presented with decreased complex I (CI) activity in the brain, suggesting that mitochondrial dysfunction accompanies Wdr45 deficiency. Overall, the systemic Wdr45 KO described here complements the two mouse models previously reported in the literature (PMIDs: 26,000,824, 31,204,559) and represents an additional robust model to investigate the pathophysiology of BPAN and to test therapeutic strategies for the disease.
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
10608 - Biochemistry and molecular biology
Result continuities
Project
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Continuities
I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace
Others
Publication year
2021
Confidentiality
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů
Data specific for result type
Name of the periodical
Mammalian Genome
ISSN
0938-8990
e-ISSN
1432-1777
Volume of the periodical
32
Issue of the periodical within the volume
5
Country of publishing house
US - UNITED STATES
Number of pages
18
Pages from-to
332-349
UT code for WoS article
000655423000001
EID of the result in the Scopus database
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