Related Experiment Video
Updated: Mar 15, 2026

Reconstruct Human Retinoblastoma In Vitro
Published on: October 11, 2022
Altered expression of retinoblastoma 1 in Hirschsprung's disease
Anne Marie O'Donnell1, David Coyle1, Prem Puri1
1National Children's Research Centre, Our Lady's Children's Hospital Crumlin, Dublin, Ireland.
Purpose:
The retinoblastoma 1 (RB1) tumor suppressor is a critical regulator of cell cycle progression and development, and has been widely documented to be inactivated in human cancer. A recent study using RB1 knockout mice suggested a new role for RB1 in the normal regulation of the enteric nervous system (ENS), because of knockout mice showing ENS abnormalities and severe intestinal dysmotility. The aim of our study was to investigate the expression of RB1 in the normal human colon and in Hirschsprung's disease (HD).
Materials And Methods:
HD tissue specimens (n=10) were collected at the time of pull-through surgery, while colonic control samples were obtained at the time of colostomy closure in patients with imperforate anus (n=10). Immunolabeling of RB1 was visualized using confocal microscopy to assess protein distribution, while western blot analysis was undertaken to quantify RB1 protein expression.
Results:
Immunohistochemistry revealed RB1 co-localized with platelet derived growth factor receptor alpha-positive (PDGFRα+) cells, nitrergic neurons and glia in controls and the ganglionic region of HD, with a marked reduction in the aganglionic HD specimens. Western blotting revealed a marked decrease in RB1 protein expression in the aganglionic region of HD colon compared to ganglionic and normal controls.
Conclusion:
We provide evidence of the presence of RB1 expression in the human colon in HD. As RB1 is known to colocalize with nitrergic neurons, the decreased expression of RB1 in the aganglionic bowel is most likely a secondary phenomenon because of the deficient nitrergic innervation in HD.
Related Concept Videos
The Retinoblastoma Gene
The first-ever tumor suppressor gene called Rb was identified in retinoblastoma - a rare eye tumor in children. In inherited forms of the disease, a child inherits one defective copy of the Rb gene, which predisposes them to retinoblastoma. However,...
The Ras Gene
Ras is a...
Hedgehog Signaling Pathway
Negative Regulator Molecules
Alternative RNA Splicing
There are five types of alternative RNA splicing that vary in the ways the pre-mRNA segments are removed or retained in the mature mRNA. The first...
Abnormal Proliferation

