The rare human intestinal disorder is due to decreased protein synthesis
Image: Phenotype analysis of Mycn mutants. The entire gut morphology is visualized via HE staining of WT and mycn mutant embryo sections at 4 dpf. Black arrows indicate goblet cells in the intestine of WT. Sections were cut along the sagittal plane.
Opinion more

Credit: Li YF et al., 2022, PLOS Biology, CC-BY 4.0 (

Decreased protein synthesis in developing gut cells contributes to a rare genetic disorder, and taking an inexpensive nutritional supplement may help reverse that decline, according to a new study published November 1.Street In the open access journal Biology Plus Written by Yun Fei Li of Zhejiang University School of Medicine in Hangzhou, China, and colleagues. This discovery is an advance in understanding the pathogenesis of the disease, and may lead to new treatments.

Feingold’s syndrome type I leads to multiple developmental problems, including the skeletal and nervous system, but the most life-affecting presentation of patients is intestinal atresia, or incomplete development of the gastrointestinal tract. The disorder results from loss-of-function mutations in the Mycn gene, which encodes a critical transcription factor that regulates the activity of many genes, but to date there is no animal model to study the effects of this loss.

The authors created this model using CRISPR genome editing to delete a portion of the Mycn gene in zebrafish, whose gut development is similar to that of humans. They found that the resulting loss in gene activity led to a significant reduction in the size of the intestine, both in length and in fold, giving the intestine its enormous surface area for absorption. Within a particularly affected subset of cells in the developing intestine, they found significant negative regulation of several ribosomal genes, resulting in reduced gene translation and protein synthesis.

Genes in the mTOR signaling pathway, a central regulator of protein synthesis, were particularly affected; Treatment of wild zebrafish with an mTOR inhibitor recapitulated the intestinal growth defects observed in Mycn mutants. When the authors treated the mutant fish with leucine, an amino acid known to activate the mTOR pathway, the result was a partial normalization of the mutants’ gut size.

Corresponding authors, Peng-Fei Xu and Xi Jin, say, “Our work shows that during embryonic development, enterocytes, which are in a highly proliferative state, require high levels of Mycn expression,” and that proliferation arrest caused by reduced protein synthesis was the main reason. For developmental defects in the gut of the Mycn mutation. This points to a potential therapeutic strategy for intestinal symptoms in patients with type 1 Feingold syndrome, although confirmation in the human intestinal organ system is necessary.”

The first authors, Yun Fei Li and Tao Cheng, add, “Feingold syndrome caused by Mycn deficiency was discovered decades ago, however, the mechanism that leads to gastrointestinal atresia in type 1 Feingold syndrome is still unclear. We developed a mutant Mycn model of fish zebrafish which recapitulates the major phenotypes of type 1 Feingold syndrome, and we have also presented a possible treatment strategy for type 1 Feingold syndrome.”


In your coverage, please use this URL to provide access to freely available paper in . format Biology Plus:

the quote: Li YF, Cheng T, Zhang YJ, Fu XX, Mo J, Zhao GQ et al. (2022) Mycn regulates intestinal growth through biogenesis of ribosomes in a zebrafish model of Feingold syndrome 1. PLoS Biol 20 (11): e3001856.

Author countries: China

Financing: The authors acknowledge the support provided by the grants of the Chinese National Key Research and Development Project (2019YFA0802402, 2018YFC1003203) and the China National Scientific Foundation (32050109, 31970757, 31900576) to PX. The funders had no role in the study design, data collection and analysis, and the decision to publish or prepare the manuscript.

Disclaimer: AAAS and EurekAlert! is not responsible for the accuracy of newsletters sent on EurekAlert! Through the contributing institutions or for the use of any information through the EurekAlert system.

Leave a Reply