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Updated: Aug 16, 2026
Cell Type-specific Gene Expression Profiling in the Mouse Liver
Published on: September 17, 2019
Impaired hepatocyte survival and liver regeneration in Atm-deficient mice
Shu Lu1, Kate C Shen, Yaolin Wang
1Barbara Ann Karmanos Cancer Institute, Wayne State University, Detroit, MI 48201, USA.
Abstract:
Atm is a stress-induced DNA damage checkpoint protein kinase with multiple roles in cell-cycle progression. Recent evidence indicates that Atm also plays a role in stem cell maintenance and self-renewal. It is not known whether Atm has a role during tissue regeneration. Using liver regeneration as a model system, we examined the role of Atm in this process. Here, we show that the expression levels of Atm protein were gradually increased during liver regeneration and this was correlated with the onset of DNA replication. The induction of Stat3 and JNK signaling, which are essential processes in normal regeneration response, was attenuated during the early phases of liver regeneration in Atm-deficient mice. P53 was transiently phosphorylated at serine 23 during liver regeneration in an Atm-dependent manner. In addition, we found that cyclin A induction was delayed and p21 was over-expressed, both of these processes were correlated with reduced and delayed DNA replication in Atm(-/-) mice during liver regeneration. Finally, we show that increased apoptosis was observed in Atm(-/-) mice in response to partial hepatectomy, indicating that Atm is required for the survival of hepatocytes. Collectively, these data indicate that liver regeneration is impaired in Atm-deficient mice. Given that liver is the first line of defense against environmental toxins, the elucidation of the function of Atm and Atm-mediated signaling pathways in liver metabolism and in response to environmental toxins is of fundamental interest.
Insights
The ATM protein kinase is crucial for liver regeneration, regulating DNA replication and hepatocyte survival. Atm deficiency impairs liver repair by disrupting key signaling pathways and increasing cell death.
Area of Science:
- Molecular Biology
- Cell Biology
- Regenerative Medicine
Background:
- ATM (Ataxia-Telangiectasia Mutated) is a DNA damage checkpoint protein kinase involved in cell-cycle progression and stem cell maintenance.
- Its role in tissue regeneration, particularly liver regeneration, remains largely unexplored.
Purpose of the Study:
- To investigate the function of ATM during liver regeneration using a mouse model.
- To elucidate the molecular mechanisms by which ATM influences hepatocyte proliferation and survival.
Main Methods:
- Analysis of ATM protein expression during liver regeneration.
- Assessment of DNA replication, cell-cycle regulators (cyclin A, p21), and signaling pathways (Stat3, JNK, p53) in wild-type and Atm-deficient mice after partial hepatectomy.
- Evaluation of hepatocyte apoptosis in response to liver injury.
Main Results:
- ATM protein levels increased during liver regeneration, correlating with DNA replication onset.
- Atm deficiency attenuated Stat3 and JNK signaling, delayed cyclin A induction, and caused p21 overexpression.
- ATM-dependent phosphorylation of p53 at serine 23 was observed.
- Reduced and delayed DNA replication, along with increased hepatocyte apoptosis, occurred in Atm-deficient mice.
- Liver regeneration was significantly impaired in Atm-deficient mice.
Conclusions:
- ATM plays a critical role in promoting hepatocyte survival and regulating DNA replication during liver regeneration.
- ATM-mediated signaling is essential for the timely and efficient execution of the liver regeneration process.
- These findings highlight the fundamental importance of ATM in liver repair and response to injury.
