University of Iowa Honors Theses

Major Department

Health and Human Physiology

College

College of Liberal Arts & Sciences

Degree

BS (Bachelor of Science)

Session and Year of Graduation

Spring 2017

Honors Major Advisor

Melissa Bates

Thesis Mentor

Fang Lin

Abstract

Congenital heart disease is the most common congenital birth defect, affecting 1.35 million newborns every year. Though therapeutic techniques have been developed to assist those afflicted, new issues arise as those that have been treated may have a higher likelihood to pass on their cardiovascular defect to their children. Adhesion G protein-coupled receptors are an increasingly studied member of the G protein-coupled receptor superfamily. aGPCRs have a wide array of molecular mechanisms that it affects; however, their role in the development of organ systems, specifically the cardiovascular system, is the focus of our research. When screening for aGPCRs within the cardiovascular system, the adgrl gene family was one family found to be expressed. Previous research has shown that various adgrl isoforms, such as adgrl2, play roles in cardiovascular development. Digoxigenin-UTP RNA probes developed through TA-vector cloning and transformation into E. coli were used to reveal mRNA expression in in-situ hybridization (ISH). ISH reveals that the adgrl isoforms 1 and 3 are expressed in the cardiovascular system, similar to adgrl2. Using CRISPR/Cas9 technology, adgrl1 and adgrl3 mutant lines were generated and, once stable, will be screened and assessed for deviant phenotypes to elucidate their role in the cardiovascular system. Additional efforts have demonstrated another gene family, bai, is expressed in dorsal forerunner cells, which influence the flow of fluid within Kupffer’s Vesicle, establishing asymmetry within the brain, gut, and heart. Mutant bai2-/- and bai2l-/- zebrafish initially demonstrated similar deviations in left-right asymmetry randomization but were eventually lost in successive generations. When stable homozygous mutants for both mutations were developed, no deviant phenotypes were observed, potentially due to their redundant roles. To assess this possibility, bai2-/- and bai2l-/- mutants were crossed and double homozygous mutants’ phenotypes will be assessed when mature.

Keywords

Congenital Heart Disease, Cardiovascular, Latrophilin, adgrl, bai, Adhesion

Total Pages

18 pages

Copyright

Copyright © 2017 Andrew Poggemiller

COinS
 

URL

http://ir.uiowa.edu/honors_theses/79