Journal article
Pax2-Islet1 Transgenic Mice Are Hyperactive and Have Altered Cerebellar Foliation
Molecular neurobiology, Vol.54(2), pp.1352-1368
03/2017
DOI: 10.1007/s12035-016-9716-6
PMCID: PMC5310572
PMID: 26843111
Abstract
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 γ-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.
Details
- Title: Subtitle
- Pax2-Islet1 Transgenic Mice Are Hyperactive and Have Altered Cerebellar Foliation
- Creators
- Romana Bohuslavova - Institute of Biotechnology CAS, Prumyslova 595, Vestec, Prague-West District, 25242, Czech RepublicNicole Dodd - Institute of Biotechnology CAS, Prumyslova 595, Vestec, Prague-West District, 25242, Czech RepublicIva Macova - Institute of Biotechnology CAS, Prumyslova 595, Vestec, Prague-West District, 25242, Czech RepublicTetyana Chumak - Institute of Experimental Medicine CAS, Prague, Czech RepublicMartin Horak - Institute of Physiology CAS, Prague, Czech RepublicJosef Syka - Institute of Experimental Medicine CAS, Prague, Czech RepublicBernd Fritzsch - Department of Biology, University of Iowa, Iowa City, IA, USAGabriela Pavlinkova - Institute of Biotechnology CAS, Prumyslova 595, Vestec, Prague-West District, 25242, Czech Republic. gpavlinkova@ibt.cas.cz
- Resource Type
- Journal article
- Publication Details
- Molecular neurobiology, Vol.54(2), pp.1352-1368
- DOI
- 10.1007/s12035-016-9716-6
- PMID
- 26843111
- PMCID
- PMC5310572
- NLM abbreviation
- Mol Neurobiol
- ISSN
- 0893-7648
- eISSN
- 1559-1182
- Publisher
- United States
- Grant note
- DOI: 10.13039/501100001824, name: Czech Science Foundation (CZ), award: 13-07996S; name: European Social Fund and the state budget of the Czech Republic, award: CZ.1.07/2.3.00/30.0020; name: EDRF, award: BIOCEV CZ.1.05/1.1.00/02.0109; DOI: 10.13039/501100001823, name: Czech Ministry of Education, Youth and Sports, award: AVOZ50520701
- Language
- English
- Date published
- 03/2017
- Academic Unit
- Iowa Neuroscience Institute; Biology; Craniofacial Anomalies Research Center
- Record Identifier
- 9984070541202771
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