ArticlePLoS genetics2015
Male-biased aganglionic megacolon in the TashT mouse line due to perturbation of silencer elements in a large gene desert of chromosome 10.
Article in PLoS genetics, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
21 citing papers in PubMed, 41 citations in OpenAlex.
- A collagen VI-dependent pathogenic mechanism for Hirschsprung's disease.The Journal of clinical investigation · 2015Trial
- Tissue and cellular spatiotemporal dynamics in colon aging.Nature biotechnology · 2026Article
- Endothelin-3 and T-type CaNature communications · 2026Article
- Single-Cell RNA Sequencing of Rabbit Sclera at Different Developmental Stages: Unveiling Scleral Cells Atlas and the Heterogeneity of Fibroblasts.Investigative ophthalmology & visual science · 2025Article
- Harnessing the Power of Enteric Glial Cells' Plasticity and Multipotency for Advancing Regenerative Medicine.International journal of molecular sciences · 2023Review
- Article
- A Single RET Mutation in Hirschsprung Disease Induces Intestinal Aganglionosis Via a Dominant-Negative Mechanism.Cellular and molecular gastroenterology and hepatology · 2023Article
- Genetic Background Influences Severity of Colonic Aganglionosis and Response to GDNF Enemas in theInternational journal of molecular sciences · 2021Article
- Bioinformatic analysis of membrane and associated proteins in murine cardiomyocytes and human myocardium.Scientific data · 2020Article
- Male-biased aganglionic megacolon in the TashT mouse model of Hirschsprung disease involves upregulation of p53 protein activity and Ddx3y gene expression.PLoS genetics · 2020Article
- Rare or Overlooked? Structural Disruption of Regulatory Domains in Human Neurocristopathies.Frontiers in genetics · 2020Review
- Molecular dissection of CHARGE syndrome highlights the vulnerability of neural crest cells to problems with alternative splicing and other transcription-related processes.Transcription · 2019Review
- Gut microbiota-mediated Gene-Environment interaction in the TashT mouse model of Hirschsprung disease.Scientific reports · 2019Article
- Dysregulation of cotranscriptional alternative splicing underlies CHARGE syndrome.Proceedings of the National Academy of Sciences of the United States of America · 2018Article
- Spatial genome organization and cognition.Nature reviews. Neuroscience · 2016Review
- Upregulation of the Nr2f1-A830082K12Rik gene pair in murine neural crest cells results in a complex phenotype reminiscent of Waardenburg syndrome type 4.Disease models & mechanisms · 2016Article
- Mouse models of Hirschsprung disease and other developmental disorders of the enteric nervous system: Old and new players.Developmental biology · 2016Review
- Gene-environment interactions and the enteric nervous system: Neural plasticity and Hirschsprung disease prevention.Developmental biology · 2016Review
- Motility: Hirschsprung disease--laying down a suitable path.Nature reviews. Gastroenterology & hepatology · 2016Article
- Pigmentation-based insertional mutagenesis is a simple and potent screening approach for identifying neurocristopathy-associated genes in mice.Rare diseases (Austin, Tex.) · 2016Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
7 authors at 2 institutions in 1 country.
Funding
Abstract
Neural crest cells (NCC) are a transient migratory cell population that generates diverse cell types such as neurons and glia of the enteric nervous system (ENS). Via an insertional mutation screen for loci affecting NCC development in mice, we identified one line-named TashT-that displays a partially penetrant aganglionic megacolon phenotype in a strong male-biased manner. Interestingly, this phenotype is highly reminiscent of human Hirschsprung's disease, a neurocristopathy with a still unexplained male sex bias. In contrast to the megacolon phenotype, colonic aganglionosis is almost fully penetrant in homozygous TashT animals. The sex bias in megacolon expressivity can be explained by the fact that the male ENS ends, on average, around a "tipping point" of minimal colonic ganglionosis while the female ENS ends, on average, just beyond it. Detailed analysis of embryonic intestines revealed that aganglionosis in homozygous TashT animals is due to slower migration of enteric NCC. The TashT insertional mutation is localized in a gene desert containing multiple highly conserved elements that exhibit repressive activity in reporter assays. RNAseq analyses and 3C assays revealed that the TashT insertion results, at least in part, in NCC-specific relief of repression of the uncharacterized gene Fam162b; an outcome independently confirmed via transient transgenesis. The transcriptional signature of enteric NCC from homozygous TashT embryos is also characterized by the deregulation of genes encoding members of the most important signaling pathways for ENS formation-Gdnf/Ret and Edn3/Ednrb-and, intriguingly, the downregulation of specific subsets of X-linked genes. In conclusion, this study not only allowed the identification of Fam162b coding and regulatory sequences as novel candidate loci for Hirschsprung's disease but also provides important new insights into its male sex bias.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.