ArticleWorld journal of gastroenterology2015
Depletion of the IKBKAP ortholog in zebrafish leads to hirschsprung disease-like phenotype.
Article in World journal of gastroenterology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.
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10 citing papers in PubMed, 16 citations in OpenAlex.
- Article
- Loss of Elp1 disrupts trigeminal ganglion neurodevelopment in a model of familial dysautonomia.eLife · 2022Article
- Association betweenTranslational pediatrics · 2022Article
- Development of the Autonomic Nervous System: Clinical Implications.Seminars in neurology · 2020Review
- Zebrafish: A Model Organism for Studying Enteric Nervous System Development and Disease.Frontiers in cell and developmental biology · 2020Review
- Potentially functional genetic variants in the TNF/TNFR signaling pathway genes predict survival of patients with non-small cell lung cancer in the PLCO cancer screening trial.Molecular carcinogenesis · 2019Article
- Advances in Enteric Neurobiology: The "Brain" in the Gut in Health and Disease.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2018Review
- [Syndromic Hirschsprung′s disease and its mode of inheritance].Zhongguo dang dai er ke za zhi = Chinese journal of contemporary pediatrics · 2018Review
- Animal and cellular models of familial dysautonomia.Clinical autonomic research : official journal of the Clinical Autonomic Research Society · 2017Review
- Hirschsprung's disease: clinical dysmorphology, genes, micro-RNAs, and future perspectives.Pediatric research · 2017Review
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Authors and funding
7 authors at 1 institution in 1 country.
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No grant is acknowledged in the PubMed record.
Abstract
aimTo 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).
methodsIn 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.
resultsWe 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.
conclusionLoss of IKBKAP contributed to HSCR as demonstrated by functional analysis in zebrafish embryos.
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