Effect of ZNF804A Knockout on A-βeta Formation in 5FAD Mice
Restricted (Penn State Only)
- Author:
- Temmer, Katherine
- Area of Honors:
- Biology
- Degree:
- Bachelor of Science
- Document Type:
- Thesis
- Thesis Supervisors:
- Yingwei Mao, Thesis Supervisor
Timothy J Jegla, Thesis Honors Advisor - Keywords:
- Biology
Neuroscience
Molecular models
Transgenic Mice
Alzheimer's disease - Abstract:
- This thesis investigates how the zinc finger binding protein 804A (ZNF), encoded by ZNF804A—a risk gene for schizophrenia and bipolar disorder—affects Alzheimer’s disease (AD) pathology in 5FAD mice. AD pathology is characterized by the presence of intraneuronal amyloid protein accumulation and extracellular deposition. The amyloid beta precursor protein, APP, forms beta pleated sheets during protein aggregation and is referred to as amyloid beta (Aβ) plaques. Previous studies on ZNF proteins have shown its effects on RNA binding, protein- protein interactions, and transcriptional and translational regulation. The full implications of ZNF have yet to be thoroughly understood or studied in the brain. However, ZNF may play a role in downstream translational effects that impact neurological functioning, such as indirect effects on lipid metabolism or lipid clearance from the brain. To understand how ZNF affects Aβ formation, knockout of the gene ZNF804A has been induced in 5FAD mice containing human APP and presenilin 1 (PSEN1) transgenes. The purpose of studying ZNF804A in AD models is to identify how it influences the expression of APP and PSEN1 transgenes, as ZNF804A proteins regulate expression of other genes related to neural development, synaptic function, and neural communication. The primary objective is to analyze whether ZNF804A knockout of one or both genes increases or decreases Aβ load in the brain. Therefore, 5FAD mice were crossed with ZNF804A mice to get 3 groups for comparison: ZNF +/+ wild type 5FAD, ZNF +/- heterozygous 5FAD, and ZNF -/- homozygous 5FAD mice. Tissue sectioning, fluorescent immunostaining, and confocal microscopy were used to quantify Aβ plaques. Results showed a significant decrease in Aβ load for ZNF -/- homozygous 5FAD mice, compared to the other groups (p-value=0.00121). This suggests that wild type ZNF804A expression exacerbates Aβ load in 5FAD mouse brains, indicating a potential therapeutic target for AD treatment.