Characterization of PAXX null mice after experimental hypoxic-ischemic brain damage and behavior studies
Mammalian cells repair DNA double-strand breaks (DSBs) by the Non-homologous DNA end-joining (NHEJ) pathway. NHEJ includes core factors, Ku70 and Ku80 effectors, XRCC4 and a ligase subunit DNA Ligase 4. In addition, there are accessory factors such as XLF, PAXX, Artemis and proteine kinase DNA-PKcs. Ku70, Ku80 and DNA-PKcs form DNA repair protein kinase complex DNA-PK. Inactivation of Ku70, Ku80, XRCC4 or Ligase 4 leads to massive p53-dependent neuronal apoptosis and immunodeficiency in mice.
Mutations in DNA-PKcs, Artemis, Xrcc4, DNA Ligase 4 and XLF genes in human results in complex syndromes characterized by immunodeficiency and neurological abnormalities. To determine an impact of mutations in PAXX gene on health, new mouse model was generated. By date, its is known that PAXX has functional redundancy with another DNA repair factor XLF. However, further details are necessary to determine specific processes explaining function of PAXX and XLF in DNA repair and its impact on health. Perinatal lethality of mice with combined deficiency for XLF and PAXX suggest role of PAXX in neurodevelopment. PAXX may play a role in protection from hypoxic ischemia, brain development, including aspects of behavior and memory.
The goal of this study is to analyze the biological significance of PAXX for development of nervous system, behavior and memory, and suppression of cancer, using knockout mouse models.
This project is supported by the Grants from Health Authority of Middle Norway, Research Council of Norway and Norwegian Cancer Society
Mutations in DNA-PKcs, Artemis, Xrcc4, DNA Ligase 4 and XLF genes in human results in complex syndromes characterized by immunodeficiency and neurological abnormalities. To determine an impact of mutations in PAXX gene on health, new mouse model was generated. By date, its is known that PAXX has functional redundancy with another DNA repair factor XLF. However, further details are necessary to determine specific processes explaining function of PAXX and XLF in DNA repair and its impact on health. Perinatal lethality of mice with combined deficiency for XLF and PAXX suggest role of PAXX in neurodevelopment. PAXX may play a role in protection from hypoxic ischemia, brain development, including aspects of behavior and memory.
The goal of this study is to analyze the biological significance of PAXX for development of nervous system, behavior and memory, and suppression of cancer, using knockout mouse models.
This project is supported by the Grants from Health Authority of Middle Norway, Research Council of Norway and Norwegian Cancer Society