Related Experiment Video

Updated: Jul 3, 2026

Intestinal Epithelial Regeneration in Response to Ionizing Irradiation
09:10

Intestinal Epithelial Regeneration in Response to Ionizing Irradiation

Published on: July 27, 2022

The intestinal epithelium compensates for p53-mediated cell death and guarantees organismal survival

Y A Valentin-Vega1, H Okano, G Lozano

  • 1Department of Genetics, Program in Genes and Development, The Graduate School of Biomedical Sciences, University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.

Cell Death and Differentiation
|July 19, 2008
PubMed

Insights

Mice lacking Mdm2 in the intestine survive but show abnormalities. The intestine compensates for Mdm2 loss by increasing proliferation and selecting against abnormal cells.

Area of Science:

  • Molecular Biology
  • Genetics
  • Gastroenterology

Background:

  • Mdm2 is a key inhibitor of the p53 tumor suppressor.
  • Loss of Mdm2 typically causes lethal phenotypes dependent on p53.
  • The function of Mdm2 in high-turnover tissues like the intestine was previously unknown.

Purpose of the Study:

  • To investigate the role of Mdm2 in the intestinal epithelium.
  • To understand the consequences of Mdm2 loss in a highly proliferative tissue.
  • To identify compensatory mechanisms in the intestine following Mdm2 deletion.

Main Methods:

  • Engineered mice lacking Mdm2 specifically in the intestinal epithelium using the Cre/LoxP system.
  • Analyzed intestinal abnormalities, apoptosis, cell populations, and signaling pathways in neonates and aged animals.

Main Results:

  • Mice lacking Mdm2 in the intestine (Mdm2(intDelta)) were viable but exhibited neonatal intestinal hyperplasia, vacuolization, and inflammation.
  • These defects were linked to increased p53-dependent apoptosis in proliferative and differentiated cells.
  • Phenotypes resolved with age as the tissue selected against Mdm2-null cells, enriched stem/progenitor populations, and increased crypt fission.
  • Enhanced proliferation was mediated by activation of Wnt and EGFR-Ras/MAPK pathways.

Conclusions:

  • Mdm2 is critical for inhibiting p53 in the intestinal epithelium.
  • The intestinal tissue possesses robust compensatory mechanisms to overcome Mdm2 loss and p53-induced apoptosis.
  • These mechanisms involve cellular selection, stem cell enrichment, and activation of pro-proliferative signaling pathways.

More Related Videos

Improved Swiss-rolling Technique for Intestinal Tissue Preparation for Immunohistochemical and Immunofluorescent Analyses07:42

Improved Swiss-rolling Technique for Intestinal Tissue Preparation for Immunohistochemical and Immunofluorescent Analyses

Published on: July 13, 2016

Protocols for Analyzing the Role of Paneth Cells in Regenerating the Murine Intestine using Conditional Cre-lox Mouse Models07:48

Protocols for Analyzing the Role of Paneth Cells in Regenerating the Murine Intestine using Conditional Cre-lox Mouse Models

Published on: November 21, 2015

Related Concept Videos

Abnormal Proliferation02:23

Abnormal Proliferation

Under normal conditions, most adult cells remain in a non-proliferative state unless stimulated by internal or external factors to replace lost cells. Abnormal cell proliferation is a condition in which the cell's growth exceeds and is uncoordinated with normal cells. In such situations, cell division persists in the same excessive manner even after cessation of the stimuli, leading to persistent tumors. The tumor arises from the damaged cells that replicate to pass the damage to the daughter...
DNA Damage can Stall the Cell Cycle02:36

DNA Damage can Stall the Cell Cycle

In response to DNA damage, cells can pause the cell cycle to assess and repair the breaks. However, the cell must check the DNA at certain critical stages during the cell cycle. If the cell cycle pauses before DNA replication, the cells will contain twice the amount of DNA. On the other hand, if cells arrest after DNA replication but before mitosis, they will contain four times the normal amount of DNA. With a host of specialized proteins at their disposal,cells must use the right protein at...
DNA Damage Can Stall the Cell Cycle02:36

DNA Damage Can Stall the Cell Cycle

In response to DNA damage, cells can pause the cell cycle to assess and repair the breaks. However, the cell must check the DNA at certain critical stages during the cell cycle. If the cell cycle pauses before DNA replication, the cells will contain twice the amount of DNA. On the other hand, if cells arrest after DNA replication but before mitosis, they will contain four times the normal amount of DNA. With a host of specialized proteins at their disposal,cells must use the right protein at...
Renewal of Intestinal Stem Cells01:23

Renewal of Intestinal Stem Cells

The intestinal epithelial lining rapidly renews every 4 to 5 days. The renewal is facilitated by intestinal stem cells (ISCs) located at the base of the crypt– a gland located at the bottom of each villus. ISCs divide asymmetrically to form new stem cells and progenitor daughter cells. The daughter cells are called transit-amplifying (TA) cells which move upwards along the crypt and either differentiate into absorptive cells– the enterocytes or secretory cells– including the goblet,...
Role Of Notch Signalling In Intestinal Stem Cell Renewal01:12

Role Of Notch Signalling In Intestinal Stem Cell Renewal

Notch signaling was first discovered in Drosophila melanogaster, where it is involved in cell lineage differentiation. Notch signaling regulates the maintenance and differentiation of intestinal stem cells or ISCs by controlling the expression of atonal homolog 1 or Atoh1. Atoh1 directs cells to differentiate into secretory cells.
Direct cell-to-cell contact is needed for the activation of Notch signaling. The signal is initiated when a notch ligand binds to a receptor on an adjacent cell, also...
Role of Ephrin-Eph Signalling in Intestinal Stem Cell Renewal01:22

Role of Ephrin-Eph Signalling in Intestinal Stem Cell Renewal

Erythropoietin-producing hepatocellular carcinoma receptor (Eph) and its ligand, Eph receptor-interacting protein (Ephrin) were first discovered in the human carcinoma cell line, hence the name. Ephrin-Eph interaction guides cells to reach their appropriate location in adult tissues. They also play an essential role in the immune system by helping in immune cell migration, adhesion, and activation. Based on their structure and function, Eph is divided into two classes — EphA and EphB.