IKAP deficiency in an FD mouse model and in oligodendrocyte precursor cells results in downregulation of genes involved in oligodendrocyte differentiation and myelin formation.

The splice site mutation in the IKBKAP gene coding for IKAP protein leads to the tissue-specific skipping of exon 20, with concomitant reduction in IKAP protein production. This causes the neurodevelopmental, autosomal-recessive genetic disorder - Familial Dysautonomia (FD). The molecular hallmark o...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	David Cheishvili, Paula Dietrich, Channa Maayan, Aviel Even, Miguel Weil, Ioannis Dragatsis, Aharon Razin
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2014
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/b07c0396ad8a461a8a1bf21f6572bd6d
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:b07c0396ad8a461a8a1bf21f6572bd6d
record_format	dspace
spelling	oai:doaj.org-article:b07c0396ad8a461a8a1bf21f6572bd6d2021-11-18T08:21:42ZIKAP deficiency in an FD mouse model and in oligodendrocyte precursor cells results in downregulation of genes involved in oligodendrocyte differentiation and myelin formation.1932-620310.1371/journal.pone.0094612https://doaj.org/article/b07c0396ad8a461a8a1bf21f6572bd6d2014-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/24760006/?tool=EBIhttps://doaj.org/toc/1932-6203The splice site mutation in the IKBKAP gene coding for IKAP protein leads to the tissue-specific skipping of exon 20, with concomitant reduction in IKAP protein production. This causes the neurodevelopmental, autosomal-recessive genetic disorder - Familial Dysautonomia (FD). The molecular hallmark of FD is the severe reduction of IKAP protein in the nervous system that is believed to be the main reason for the devastating symptoms of this disease. Our recent studies showed that in the brain of two FD patients, genes linked to oligodendrocyte differentiation and/or myelin formation are significantly downregulated, implicating IKAP in the process of myelination. However, due to the scarcity of FD patient tissues, these results awaited further validation in other models. Recently, two FD mouse models that faithfully recapitulate FD were generated, with two types of mutations resulting in severely low levels of IKAP expression. Here we demonstrate that IKAP deficiency in these FD mouse models affects a similar set of genes as in FD patients' brains. In addition, we identified two new IKAP target genes involved in oligodendrocyte cells differentiation and myelination, further underscoring the essential role of IKAP in this process. We also provide proof that IKAP expression is needed cell-autonomously for the regulation of expression of genes involved in myelin formation since knockdown of IKAP in the Oli-neu oligodendrocyte precursor cell line results in similar deficiencies. Further analyses of these two experimental models will compensate for the lack of human postmortem tissues and will advance our understanding of the role of IKAP in myelination and the disease pathology.David CheishviliPaula DietrichChanna MaayanAviel EvenMiguel WeilIoannis DragatsisAharon RazinPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 9, Iss 4, p e94612 (2014)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q David Cheishvili Paula Dietrich Channa Maayan Aviel Even Miguel Weil Ioannis Dragatsis Aharon Razin IKAP deficiency in an FD mouse model and in oligodendrocyte precursor cells results in downregulation of genes involved in oligodendrocyte differentiation and myelin formation.
description	The splice site mutation in the IKBKAP gene coding for IKAP protein leads to the tissue-specific skipping of exon 20, with concomitant reduction in IKAP protein production. This causes the neurodevelopmental, autosomal-recessive genetic disorder - Familial Dysautonomia (FD). The molecular hallmark of FD is the severe reduction of IKAP protein in the nervous system that is believed to be the main reason for the devastating symptoms of this disease. Our recent studies showed that in the brain of two FD patients, genes linked to oligodendrocyte differentiation and/or myelin formation are significantly downregulated, implicating IKAP in the process of myelination. However, due to the scarcity of FD patient tissues, these results awaited further validation in other models. Recently, two FD mouse models that faithfully recapitulate FD were generated, with two types of mutations resulting in severely low levels of IKAP expression. Here we demonstrate that IKAP deficiency in these FD mouse models affects a similar set of genes as in FD patients' brains. In addition, we identified two new IKAP target genes involved in oligodendrocyte cells differentiation and myelination, further underscoring the essential role of IKAP in this process. We also provide proof that IKAP expression is needed cell-autonomously for the regulation of expression of genes involved in myelin formation since knockdown of IKAP in the Oli-neu oligodendrocyte precursor cell line results in similar deficiencies. Further analyses of these two experimental models will compensate for the lack of human postmortem tissues and will advance our understanding of the role of IKAP in myelination and the disease pathology.
format	article
author	David Cheishvili Paula Dietrich Channa Maayan Aviel Even Miguel Weil Ioannis Dragatsis Aharon Razin
author_facet	David Cheishvili Paula Dietrich Channa Maayan Aviel Even Miguel Weil Ioannis Dragatsis Aharon Razin
author_sort	David Cheishvili
title	IKAP deficiency in an FD mouse model and in oligodendrocyte precursor cells results in downregulation of genes involved in oligodendrocyte differentiation and myelin formation.
title_short	IKAP deficiency in an FD mouse model and in oligodendrocyte precursor cells results in downregulation of genes involved in oligodendrocyte differentiation and myelin formation.
title_full	IKAP deficiency in an FD mouse model and in oligodendrocyte precursor cells results in downregulation of genes involved in oligodendrocyte differentiation and myelin formation.
title_fullStr	IKAP deficiency in an FD mouse model and in oligodendrocyte precursor cells results in downregulation of genes involved in oligodendrocyte differentiation and myelin formation.
title_full_unstemmed	IKAP deficiency in an FD mouse model and in oligodendrocyte precursor cells results in downregulation of genes involved in oligodendrocyte differentiation and myelin formation.
title_sort	ikap deficiency in an fd mouse model and in oligodendrocyte precursor cells results in downregulation of genes involved in oligodendrocyte differentiation and myelin formation.
publisher	Public Library of Science (PLoS)
publishDate	2014
url	https://doaj.org/article/b07c0396ad8a461a8a1bf21f6572bd6d
work_keys_str_mv	AT davidcheishvili ikapdeficiencyinanfdmousemodelandinoligodendrocyteprecursorcellsresultsindownregulationofgenesinvolvedinoligodendrocytedifferentiationandmyelinformation AT pauladietrich ikapdeficiencyinanfdmousemodelandinoligodendrocyteprecursorcellsresultsindownregulationofgenesinvolvedinoligodendrocytedifferentiationandmyelinformation AT channamaayan ikapdeficiencyinanfdmousemodelandinoligodendrocyteprecursorcellsresultsindownregulationofgenesinvolvedinoligodendrocytedifferentiationandmyelinformation AT avieleven ikapdeficiencyinanfdmousemodelandinoligodendrocyteprecursorcellsresultsindownregulationofgenesinvolvedinoligodendrocytedifferentiationandmyelinformation AT miguelweil ikapdeficiencyinanfdmousemodelandinoligodendrocyteprecursorcellsresultsindownregulationofgenesinvolvedinoligodendrocytedifferentiationandmyelinformation AT ioannisdragatsis ikapdeficiencyinanfdmousemodelandinoligodendrocyteprecursorcellsresultsindownregulationofgenesinvolvedinoligodendrocytedifferentiationandmyelinformation AT aharonrazin ikapdeficiencyinanfdmousemodelandinoligodendrocyteprecursorcellsresultsindownregulationofgenesinvolvedinoligodendrocytedifferentiationandmyelinformation
_version_	1718421881794592768

IKAP deficiency in an FD mouse model and in oligodendrocyte precursor cells results in downregulation of genes involved in oligodendrocyte differentiation and myelin formation.

Ejemplares similares