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Atm and c-Abl cooperate in the response to genotoxic stress during nervous system development

Heather L Miller1, Youngsoo Lee, Jingfeng Zhao

  • 1Department of Genetics, St. Jude Children's Research Hospital, 332N Lauderdale, Memphis, TN 38105, USA.

Brain Research. Developmental Brain Research
|October 2, 2003
PubMed

Insights

The ATM kinase and c-Abl proto-oncogene are crucial for mouse development and neural integrity. Genetic inactivation revealed their essential roles in preventing midgestational lethality and neurodevelopmental abnormalities.

Area of Science:

  • Genetics
  • Molecular Biology
  • Developmental Biology

Background:

  • The ATM kinase targets the c-Abl proto-oncogene following DNA double-strand breaks.
  • The precise physiological roles of ATM and c-Abl in development remain unclear.

Purpose of the Study:

  • To investigate the functions of c-Abl and ATM during mouse development.
  • To understand the interplay between c-Abl and ATM signaling pathways.

Main Methods:

  • Generation of mice with combined c-Abl and Atm mutant alleles.
  • Analysis of developmental outcomes and neurodevelopmental abnormalities in mutant mice.

Main Results:

  • Dual inactivation of Atm and c-Abl typically led to midgestational lethality.
  • Mice with three mutant alleles (c-Abl(-/-)Atm(+/-) or c-Abl(+/-)Atm(-/-)) were viable but showed increased susceptibility to neurodevelopmental issues after genotoxic stress.

Conclusions:

  • These findings establish a genetic link between ATM and c-Abl signaling pathways.
  • The study highlights a significant interrelationship between ATM and c-Abl in neural development.

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