Related Experiment Video

Updated: Aug 21, 2026

A Seminiferous Tubule Squash Technique for the Cytological Analysis of Spermatogenesis Using the Mouse Model
09:40

A Seminiferous Tubule Squash Technique for the Cytological Analysis of Spermatogenesis Using the Mouse Model

Published on: February 6, 2018

The mammalian mid-pachytene checkpoint: meiotic arrest in spermatocytes with a mutation in Atm alone or in

T Ashley1, C Westphal, A Plug-de Maggio

  • 1Department of Genetics, Yale University School of Medicine, New Haven, CT 06510, USA. terry.ashley@syale.edu

Cytogenetic and Genome Research
|October 7, 2004
PubMed

Insights

ATM (ataxia-telangiectasia mutated) protein is crucial for DNA repair and cell cycle control. Disabling ATM causes male sterility in mice, and p53 or p21 gene disruption does not rescue this defect.

Area of Science:

  • Molecular Biology
  • Genetics
  • Cell Biology

Background:

  • ATM (ataxia-telangiectasia mutated) is a key protein kinase in DNA double-strand break (DSB) repair and cell cycle checkpoint control.
  • ATM plays a critical role in phosphorylating downstream targets like p53, regulating cellular responses to DNA damage in somatic cells.
  • Mutations in ATM cause the human disorder ataxia-telangiectasia, characterized by neurodegeneration and cancer predisposition.

Purpose of the Study:

  • To investigate the role of ATM in male germ cell development and its interaction with the p53 pathway.
  • To determine if disrupting the p53 or p21 pathway can rescue the male sterility phenotype observed in Atm-deficient mice.

Main Methods:

  • Analysis of Atm-deficient mouse models.
  • Examination of testicular histology and cell apoptosis.
  • Genetic disruption of Trp53 (p53) and Cdkn1a (p21/Cip1) genes in Atm-deficient backgrounds.

Main Results:

  • Atm-deficient mice exhibit male sterility due to arrest and apoptosis of spermatocytes at stage IV (mid-pachynema).
  • Disruption of the Trp53 (p53) gene did not rescue the male sterility or spermatogenic defects in Atm-deficient mice.
  • Downstream target Cdkn1a (p21/Cip1) disruption also failed to ameliorate the Atm-related reproductive defect.

Conclusions:

  • The p53 and p21 pathways are not essential for mediating the male sterile phenotype in Atm-deficient mice.
  • ATM's role in male germ cell development is distinct from its function in somatic cells regarding p53/p21 regulation.
  • These findings highlight the complex and tissue-specific functions of ATM in mammalian reproduction and DNA damage response.

More Related Videos

Evaluation of the Spindle Assembly Checkpoint Integrity in Mouse Oocytes10:09

Evaluation of the Spindle Assembly Checkpoint Integrity in Mouse Oocytes

Published on: September 13, 2022

Functional Assessment of Kinesin-7 CENP-E in Spermatocytes Using In Vivo Inhibition, Immunofluorescence and Flow Cytometry09:41

Functional Assessment of Kinesin-7 CENP-E in Spermatocytes Using In Vivo Inhibition, Immunofluorescence and Flow Cytometry

Published on: December 28, 2021

Related Concept Videos

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...
The Spindle Assembly Checkpoint02:19

The Spindle Assembly Checkpoint

The spindle assembly checkpoint is a molecular surveillance mechanism ensuring the fidelity of chromosome segregation during anaphase. The checkpoint monitors the completion of all the prerequisite steps before chromosome segregation to determine whether the segregation process should proceed or be delayed.
Many proteins function together to control the spindle assembly checkpoint. Mutations affecting these proteins may allow cells to proceed into anaphase prematurely, resulting in the...
Meiosis II02:02

Meiosis II

Meiosis II entails cell division and segregation of the sister chromatids, resulting in the production of four unique haploid gametes. The steps for meiosis II are similar to mitosis, except that meiosis II occurs in haploid cells, whereas mitosis occurs in diploid cells.
The timing and cell division patterns of meiosis differ between males and females. In male meiosis, the centrosomes are part of the formation of the meiotic spindle. However, in oocytes, including that of humans, Drosophila,...
Meiosis II01:57

Meiosis II

Meiosis II is the second and final stage of meiosis. It relies on the haploid cells produced during meiosis I, each of which contain only 23 chromosomes—one from each homologous initial pair. Importantly, each chromosome in these cells is composed of two joined copies, and when these cells enter meiosis II, the goal is to separate such sister chromatids using the same microtubule-based network employed in other division processes. The result of meiosis II is two haploid cells, each containing...
Separation of Sister Chromatids02:17

Separation of Sister Chromatids

At the transition from prophase to metaphase, there is a reduction in cohesion along the chromosomal arms, resulting in the resolution of sister chromatids. However, residual cohesin connections remain to hold the sister chromatids together until the transition from metaphase to anaphase. The residual connection prevents any premature separation of sister chromatids, blocking the risks of aneuploidy within the daughter cells.
At the onset of anaphase, separase, a proteolytic enzyme, is...