Dissertations and Theses

Date of Award

2019

Document Type

Thesis

Department

Biology

First Advisor

Chrsitine Li

Second Advisor

Jonathan Levitt

Third Advisor

Itzhek Mano

Keywords

male tail morphogenesis nematode alzheimer's mating

Abstract

Alzheimer's disease is a neurodegenerative disease that affects more than 30 million people globally. The disease is characterized by an accumulation of extracellular beta-amyloid peptide plaques and intracellular neurofibrillary tangles in the brain. The beta-amyloid peptide is derived from a larger precursor protein, the amyloid precursor protein (APP). Mutations in APP have been correlated with Alzheimer's disease. Due to the presence of two paralogues, APLP1 and APLP2, which have overlapping functions, the normal function of APP is difficult to elucidate. Knockout of the entire APP gene family in mice results in lethality and developmental defects, indicating that the APP gene family has an essential function. The nematode Caenorhabditis elegans has one APP ortholog, apl-1. apl-1(yn10) knockouts are not viable, indicating that apl-1 has an essential function. apl-1(yn5) is a temperature sensitive allele; these mutants produce only the extracellular domain of APL-1. At the permissive temperature apl-1(yn5) mutants have many phenotypic defects, which include poor mating and delayed development; at the restrictive temperature, apl-1(yn5) mutants show an incompletely penetrant lethality. moa-1 mutations suppress the apl-1(yn5) lethality at the restrictive temperature. Surprisingly, moa-1 is involved in male tail development; the male tail is critical for successful mating. This project focused on studying the morphology and mating behavior of yn5 mutants, moa-1 transgenic animals, and other mutants regulating male tail development. Strains were characterized for morphology and mating behavior without knowledge of the genotype of the animals. Understanding male tail development may provide insights into other pathways in which apl-1 functions.

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