ATRX Mutations In IDH1-Mutated Mice Neural Stem Cells
School Name
South Carolina Governor's School for Science & Mathematics
Grade Level
12th Grade
Presentation Topic
Cell and Molecular Biology
Presentation Type
Mentored
Oral Presentation Award
3rd Place
Abstract
The WHO altered their diagnostic methods for central nervous system tumors. These diagnostic methods now include both histologic analysis of the tumor cells and determination of genetic mutations present. IDH1-mutations in astrocytoma lead to the production of 2-hydroxyglutarate, which inhibits proteins that are important in cellular metabolism. When the metabolism is abnormal, cells can divide too quickly and form tumors. An accurate mouse model of neural cells with the IDH1 mutations does not yet exist for therapeutic research. We hypothesized that coupling IDH1 mutations with the two other characteristic mutations in astrocytoma—p53 and ATRX—would create a functional dependency and improved model. p53 is known primarily as a tumor suppressor gene that causes cell cycle arrest when there is DNA damage. ATRX mutation is important to development, and mutations can cause either mental retardation or cancer, but its specific function remains unknown. ATRX mutations were inserted into mice neural stem cells, and the cellular functions and rate of division were monitored with ATRX, p53, and IDH1 mutations were combined. Western Blot and Immunofluorescence were used to measure protein levels and efficacy of the induction. ATRX was shown to have a positive effect on the levels of proliferation in IDH1 and p53 mutated cells. This is the first sign of cancerous behavior, and thus suggests that there is a sequence that the mutations arise in astrocytoma. This research can be used to better understand the function of these lesser known mutations and improve the mouse models used for clinical studies.
Recommended Citation
Scopano, Layne, "ATRX Mutations In IDH1-Mutated Mice Neural Stem Cells" (2019). South Carolina Junior Academy of Science. 57.
https://scholarexchange.furman.edu/scjas/2019/all/57
Location
Founders Hall 114 A
Start Date
3-30-2019 10:15 AM
Presentation Format
Oral and Written
Group Project
No
ATRX Mutations In IDH1-Mutated Mice Neural Stem Cells
Founders Hall 114 A
The WHO altered their diagnostic methods for central nervous system tumors. These diagnostic methods now include both histologic analysis of the tumor cells and determination of genetic mutations present. IDH1-mutations in astrocytoma lead to the production of 2-hydroxyglutarate, which inhibits proteins that are important in cellular metabolism. When the metabolism is abnormal, cells can divide too quickly and form tumors. An accurate mouse model of neural cells with the IDH1 mutations does not yet exist for therapeutic research. We hypothesized that coupling IDH1 mutations with the two other characteristic mutations in astrocytoma—p53 and ATRX—would create a functional dependency and improved model. p53 is known primarily as a tumor suppressor gene that causes cell cycle arrest when there is DNA damage. ATRX mutation is important to development, and mutations can cause either mental retardation or cancer, but its specific function remains unknown. ATRX mutations were inserted into mice neural stem cells, and the cellular functions and rate of division were monitored with ATRX, p53, and IDH1 mutations were combined. Western Blot and Immunofluorescence were used to measure protein levels and efficacy of the induction. ATRX was shown to have a positive effect on the levels of proliferation in IDH1 and p53 mutated cells. This is the first sign of cancerous behavior, and thus suggests that there is a sequence that the mutations arise in astrocytoma. This research can be used to better understand the function of these lesser known mutations and improve the mouse models used for clinical studies.
