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Article: Depletion of the IKBKAP ortholog in zebrafish leads to hirschsprung disease-like phenotype

TitleDepletion of the IKBKAP ortholog in zebrafish leads to hirschsprung disease-like phenotype
Authors
KeywordsEnteric nervous system
Zebrafish
Morpholinos
IKBKAP
Hirschsprung disease
Issue Date2015
Citation
World Journal of Gastroenterology, 2015, v. 21, n. 7, p. 2040-2046 How to Cite?
Abstract© The Author(s) 2015. Published by Baishideng Publishing Group Inc. All rights reserved. AIM: To investigate the role of IKBKAP (inhibitor of kappa light polypeptide gene enhancer in B-cells, kinase complex-associated protein) in the development of enteric nervous system (ENS) and Hirschsprung disease (HSCR). METHODS: In this study, we injected a morpholino that blocked the translation of ikbkap protein to 1-cell stage zebrafish embryos. The phenotype in the ENS was analysed by antibody staining of the pan-neuronal marker HuC/D followed by enteric neuron counting. The mean numbers of enteric neurons were compared between the morphant and the control. We also studied the expressions of ret and phox2bb, which are involved in ENS development, in the ikbkap morpholino injected embryos by quantitative reverse transcriptase polymerase chain reaction and compared them with the control. RESULTS: We observed aganglionosis (χ2, P < 0.01) and a reduced number of enteric neurons (38.8 ± 9.9 vs 50.2 ± 17.3, P < 0.05) in the zebrafish embryos injected with ikbkap translation-blocking morpholino (morphant) when compared with the control embryos. Specificity of the morpholino was confirmed by similar results obtained using a second non-overlapping morpholino that blocked the translation of ikbkap. We further studied the morphant by analysing the expression levels of genes involved in ENS development such as ret, phox2bb and sox10, and found that phox2bb, the ortholog of human PHOX2B, was significantly down-regulated (0.51 ± 0.15 vs 1.00 ± 0, P < 0.05). Although we also observed a reduction in the expression of ret, the difference was not significant. CONCLUSION: Loss of IKBKAP contributed to HSCR as demonstrated by functional analysis in zebrafish embryos.
Persistent Identifierhttp://hdl.handle.net/10722/220727
ISSN
2015 Impact Factor: 2.787
2015 SCImago Journal Rankings: 1.076
PubMed Central ID

 

DC FieldValueLanguage
dc.contributor.authorCheng, William Wai Chun-
dc.contributor.authorTang, Clara Sze Man-
dc.contributor.authorGui, Hong Sheng-
dc.contributor.authorSo, Man Ting-
dc.contributor.authorLui, Vincent Chi Hang-
dc.contributor.authorTam, Paul Kwong Hang-
dc.contributor.authorGarcia-Barcelo, Maria Mercè-
dc.date.accessioned2015-10-16T06:50:23Z-
dc.date.available2015-10-16T06:50:23Z-
dc.date.issued2015-
dc.identifier.citationWorld Journal of Gastroenterology, 2015, v. 21, n. 7, p. 2040-2046-
dc.identifier.issn1007-9327-
dc.identifier.urihttp://hdl.handle.net/10722/220727-
dc.description.abstract© The Author(s) 2015. Published by Baishideng Publishing Group Inc. All rights reserved. AIM: To investigate the role of IKBKAP (inhibitor of kappa light polypeptide gene enhancer in B-cells, kinase complex-associated protein) in the development of enteric nervous system (ENS) and Hirschsprung disease (HSCR). METHODS: In this study, we injected a morpholino that blocked the translation of ikbkap protein to 1-cell stage zebrafish embryos. The phenotype in the ENS was analysed by antibody staining of the pan-neuronal marker HuC/D followed by enteric neuron counting. The mean numbers of enteric neurons were compared between the morphant and the control. We also studied the expressions of ret and phox2bb, which are involved in ENS development, in the ikbkap morpholino injected embryos by quantitative reverse transcriptase polymerase chain reaction and compared them with the control. RESULTS: We observed aganglionosis (χ2, P < 0.01) and a reduced number of enteric neurons (38.8 ± 9.9 vs 50.2 ± 17.3, P < 0.05) in the zebrafish embryos injected with ikbkap translation-blocking morpholino (morphant) when compared with the control embryos. Specificity of the morpholino was confirmed by similar results obtained using a second non-overlapping morpholino that blocked the translation of ikbkap. We further studied the morphant by analysing the expression levels of genes involved in ENS development such as ret, phox2bb and sox10, and found that phox2bb, the ortholog of human PHOX2B, was significantly down-regulated (0.51 ± 0.15 vs 1.00 ± 0, P < 0.05). Although we also observed a reduction in the expression of ret, the difference was not significant. CONCLUSION: Loss of IKBKAP contributed to HSCR as demonstrated by functional analysis in zebrafish embryos.-
dc.languageeng-
dc.relation.ispartofWorld Journal of Gastroenterology-
dc.subjectEnteric nervous system-
dc.subjectZebrafish-
dc.subjectMorpholinos-
dc.subjectIKBKAP-
dc.subjectHirschsprung disease-
dc.titleDepletion of the IKBKAP ortholog in zebrafish leads to hirschsprung disease-like phenotype-
dc.typeArticle-
dc.description.natureLink_to_subscribed_fulltext-
dc.identifier.doi10.3748/wjg.v21.i7.2040-
dc.identifier.pmcidPMC4326138-
dc.identifier.scopuseid_2-s2.0-84922731712-
dc.identifier.hkuros242703-
dc.identifier.volume21-
dc.identifier.issue7-
dc.identifier.spage2040-
dc.identifier.epage2046-
dc.identifier.eissn2219-2840-

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