Date of Award

January 2021

Document Type

Open Access Thesis

Degree Name

Master of Public Health (MPH)

Department

School of Public Health

First Advisor

Josephine Hoh

Abstract

Age-related macular degeneration (AMD) is the most common cause of central vision loss in developed world. Two genes on chromosome 10q26, maculopathy susceptibility 2 (ARMS2) and HtrA serine peptidase 1 (HTRA1) were identified as candidate genetic factors of AMD. However, due to the high linkage disequilibrium across the locus as well as the inconsistent functional findings regarding the two genes, it is difficult to distinguish the causative gene that confer the risk of AMD. To provide insight of the functional roles of ARMS2 and HTRA1 in the pathogenesis of AMD, we investigated the regulation relationship between the two genes in vivo. To overcome the difficulty that ARMS2 gene only exists in higher primates, we generated humanized ARMS2 knock-in mice. Human ARMS2 cDNA was inserted into the corresponding locus upstream the Htra1 gene in mouse genome. Decline of Htra1 gene expression was found in the cortex of ARMS2 KI mice using RT-qPCR technique. Our finding indicates the presence of ARMS2 gene upstream Htra1 may manifest negative regulation effect upon Htra1 expression. This new evidence revealed the complexity of how the two genes might work together in the causal pathway of AMD. Furthermore, we provided a novel and valuable animal model that could facilitate further research of AMD pathogenesis.

Comments

This is an Open Access Thesis.

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