Pax2-Islet1 Transgenic Mice Are Hyperactive and Have Altered Cerebellar Foliation

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F68378041%3A_____%2F17%3A00474451" target="_blank" >RIV/68378041:_____/17:00474451 - isvavai.cz</a>

Nalezeny alternativní kódy

RIV/86652036:_____/17:00474451 RIV/67985823:_____/17:00474451

Výsledek na webu

<a href="http://dx.doi.org/10.1007/s12035-016-9716-6" target="_blank" >http://dx.doi.org/10.1007/s12035-016-9716-6</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1007/s12035-016-9716-6" target="_blank" >10.1007/s12035-016-9716-6</a>

Jazyk výsledku

angličtina

Název v původním jazyce

Pax2-Islet1 Transgenic Mice Are Hyperactive and Have Altered Cerebellar Foliation

Popis výsledku v původním jazyce

The programming of cell fate by transcription factors requires precise regulation of their time and level of expression. The LIM-homeodomain transcription factor Islet1 (Isl1) is involved in cell-fate specification of motor neurons, and it may play a similar role in the inner ear. In order to study its role in the regulation of vestibulo-motor development, we investigated a transgenic mouse expressing Isl1 under the Pax2 promoter control (Tg (+/-) ). The transgenic mice show altered level, time, and place of expression of Isl1 but are viable. However, Tg (+/-) mice exhibit hyperactivity, including circling behavior, and progressive age-related decline in hearing, which has been reported previously. Here, we describe the molecular and morphological changes in the cerebellum and vestibular system that may cause the hyperactivity of Tg (+/-) mice. The transgene altered the formation of folia in the cerebellum, the distribution of calretinin labeled unipolar brush cells, and reduced the size of the cerebellum, inferior colliculus, and saccule. Age-related progressive reduction of calbindin expression was detected in Purkinje cells in the transgenic cerebella. The hyperactivity of Tg (+/-) mice is reduced upon the administration of picrotoxin, a non-competitive channel blocker for the gamma-aminobutyric acid (GABA) receptor chloride channels. This suggests that the overexpression of Isl1 significantly affects the functions of GABAergic neurons. We demonstrate that the overexpression of Isl1 affects the development and function of the cerebello-vestibular system, resulting in hyperactivity.

Název v anglickém jazyce

Pax2-Islet1 Transgenic Mice Are Hyperactive and Have Altered Cerebellar Foliation

Popis výsledku anglicky

The programming of cell fate by transcription factors requires precise regulation of their time and level of expression. The LIM-homeodomain transcription factor Islet1 (Isl1) is involved in cell-fate specification of motor neurons, and it may play a similar role in the inner ear. In order to study its role in the regulation of vestibulo-motor development, we investigated a transgenic mouse expressing Isl1 under the Pax2 promoter control (Tg (+/-) ). The transgenic mice show altered level, time, and place of expression of Isl1 but are viable. However, Tg (+/-) mice exhibit hyperactivity, including circling behavior, and progressive age-related decline in hearing, which has been reported previously. Here, we describe the molecular and morphological changes in the cerebellum and vestibular system that may cause the hyperactivity of Tg (+/-) mice. The transgene altered the formation of folia in the cerebellum, the distribution of calretinin labeled unipolar brush cells, and reduced the size of the cerebellum, inferior colliculus, and saccule. Age-related progressive reduction of calbindin expression was detected in Purkinje cells in the transgenic cerebella. The hyperactivity of Tg (+/-) mice is reduced upon the administration of picrotoxin, a non-competitive channel blocker for the gamma-aminobutyric acid (GABA) receptor chloride channels. This suggests that the overexpression of Isl1 significantly affects the functions of GABAergic neurons. We demonstrate that the overexpression of Isl1 affects the development and function of the cerebello-vestibular system, resulting in hyperactivity.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

10605 - Developmental biology

Projekt

Výsledek vznikl pri realizaci vícero projektů. Více informací v záložce Projekty.

Návaznosti

P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)

Rok uplatnění

2017

Kód důvěrnosti údajů

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

Název periodika

Molecular Neurobiology

ISSN

0893-7648

e-ISSN

—

Svazek periodika

54

Číslo periodika v rámci svazku

2

Stát vydavatele periodika

US - Spojené státy americké

Počet stran výsledku

17

Strana od-do

1352-1368

Kód UT WoS článku

000394964100046

EID výsledku v databázi Scopus

2-s2.0-84957574582