Glycogen Storage Disorder (GSD Ia) is a rare and lethal autosomal recessive genetic disorder with no current treatment. This disorder is caused by a deficiency in the G6PC1 gene, primarily expressed in the liver, kidney, and intestine. The G6PC1 gene codifies for the G6Pase-alpha protein that is responsible for breaking down glycogen into glucose. Without the G6PC1 gene, glycogen builds up in the liver and multiple complications soon follow. This includes hypoglycemia (low glucose levels), hepatomegaly (enlargement of the liver), and benign and/or malignant tumors.
My project will first focus on developing and verifying a mouse model with GSD Ia by deleting G6PC1 gene in exclusively hepatocytes (liver cells). From here, we could go even further and establish a humanized mouse model by injecting G6PC1-deficient human hepatocytes into the mouse’s liver and allowing repopulation. By creating this model, we can conduct GSD Ia experiments with human hepatocytes in vivo without the risking the lives of human patients!
To verify that this model is a valid representation of GSD Ia, we need to verify the deletion of the G6PC1gene. Evidence of hypoglycemia is sufficient to prove this. Polymerase Chain Reaction (PCR) Test, Immunohistochemistry and Immunofluorescence Analysis, and glucose level testing can be used in turn to validate hypoglycemia.
If the results come back positive for hypoglycemia and the model is verified, we can then begin therapeutic research!
Very cool! This sounds like a very important and exciting project. Great job explaining the terms.