Generation and Characterization of a Novel Angelman Syndrome Mouse Model with a Full Deletion of the Ube3a Gene

Result code in IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F68378050%3A_____%2F22%3A00561877" target="_blank" >RIV/68378050:_____/22:00561877 - isvavai.cz</a>

Result on the web

<a href="https://www.mdpi.com/2073-4409/11/18/2815" target="_blank" >https://www.mdpi.com/2073-4409/11/18/2815</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.3390/cells11182815" target="_blank" >10.3390/cells11182815</a>

Result language

angličtina

Original language name

Generation and Characterization of a Novel Angelman Syndrome Mouse Model with a Full Deletion of the Ube3a Gene

Original language description

Angelman syndrome (AS) is a neurodevelopmental disorder caused by deficits in maternally inherited UBE3A. The disease is characterized by intellectual disability, impaired motor skills, and behavioral deficits, including increased anxiety and autism spectrum disorder features. The mouse models used so far in AS research recapitulate most of the cardinal AS characteristics. However, they do not mimic the situation found in the majority of AS patients who have a large deletion spanning 4-6 Mb. There is also a large variability in phenotypes reported in the available models, which altogether limits development of therapeutics. Therefore, we have generated a mouse model in which the Ube3a gene is deleted entirely from the 5 ' UTR to the 3 ' UTR of mouse Ube3a isoform 2, resulting in a deletion of 76 kb. To investigate its phenotypic suitability as a model for AS, we employed a battery of behavioral tests directed to reveal AS pathology and to find out whether this model better mirrors AS development compared to other available models. We found that the maternally inherited Ube3a-deficient line exhibits robust motor dysfunction, as seen in the rotarod and DigiGait tests, and displays abnormalities in additional behavioral paradigms, including reduced nest building and hypoactivity, although no apparent cognitive phenotype was observed in the Barnes maze and novel object recognition tests. The AS mice did, however, underperform in more complex cognition tasks, such as place reversal in the IntelliCage system, and exhibited a different circadian rhythm activity pattern. We show that the novel UBE3A-deficient model, based on a whole-gene deletion, is suitable for AS research, as it recapitulates important phenotypes characteristic of AS. This new mouse model provides complementary possibilities to study the Ube3a gene and its function in health and disease as well as possible therapeutic interventions to restore function.

Czech name

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Czech description

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Type

J_imp - Article in a specialist periodical, which is included in the Web of Science database

CEP classification

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OECD FORD branch

10601 - Cell biology

Project

Result was created during the realization of more than one project. More information in the Projects tab.

Continuities

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Publication year

2022

Confidentiality

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Name of the periodical

Cells

ISSN

2073-4409

e-ISSN

2073-4409

Volume of the periodical

11

Issue of the periodical within the volume

18

Country of publishing house

CH - SWITZERLAND

Number of pages

20

Pages from-to

2815

UT code for WoS article

000857687800001

EID of the result in the Scopus database

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