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Pax2-Islet1 Transgenic Mice Are Hyperactive and Have Altered Cerebellar Foliation
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...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Springer US
2016
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5310572/ https://www.ncbi.nlm.nih.gov/pubmed/26843111 http://dx.doi.org/10.1007/s12035-016-9716-6 |
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author | Bohuslavova, Romana Dodd, Nicole Macova, Iva Chumak, Tetyana Horak, Martin Syka, Josef Fritzsch, Bernd Pavlinkova, Gabriela |
author_facet | Bohuslavova, Romana Dodd, Nicole Macova, Iva Chumak, Tetyana Horak, Martin Syka, Josef Fritzsch, Bernd Pavlinkova, Gabriela |
author_sort | Bohuslavova, Romana |
collection | PubMed |
description | 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. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s12035-016-9716-6) contains supplementary material, which is available to authorized users. |
format | Online Article Text |
id | pubmed-5310572 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2016 |
publisher | Springer US |
record_format | MEDLINE/PubMed |
spelling | pubmed-53105722017-02-28 Pax2-Islet1 Transgenic Mice Are Hyperactive and Have Altered Cerebellar Foliation Bohuslavova, Romana Dodd, Nicole Macova, Iva Chumak, Tetyana Horak, Martin Syka, Josef Fritzsch, Bernd Pavlinkova, Gabriela Mol Neurobiol Article 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. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s12035-016-9716-6) contains supplementary material, which is available to authorized users. Springer US 2016-02-03 2017 /pmc/articles/PMC5310572/ /pubmed/26843111 http://dx.doi.org/10.1007/s12035-016-9716-6 Text en © The Author(s) 2016 Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. |
spellingShingle | Article Bohuslavova, Romana Dodd, Nicole Macova, Iva Chumak, Tetyana Horak, Martin Syka, Josef Fritzsch, Bernd Pavlinkova, Gabriela Pax2-Islet1 Transgenic Mice Are Hyperactive and Have Altered Cerebellar Foliation |
title | Pax2-Islet1 Transgenic Mice Are Hyperactive and Have Altered Cerebellar Foliation |
title_full | Pax2-Islet1 Transgenic Mice Are Hyperactive and Have Altered Cerebellar Foliation |
title_fullStr | Pax2-Islet1 Transgenic Mice Are Hyperactive and Have Altered Cerebellar Foliation |
title_full_unstemmed | Pax2-Islet1 Transgenic Mice Are Hyperactive and Have Altered Cerebellar Foliation |
title_short | Pax2-Islet1 Transgenic Mice Are Hyperactive and Have Altered Cerebellar Foliation |
title_sort | pax2-islet1 transgenic mice are hyperactive and have altered cerebellar foliation |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5310572/ https://www.ncbi.nlm.nih.gov/pubmed/26843111 http://dx.doi.org/10.1007/s12035-016-9716-6 |
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