Investigating the role of MRPL40 in cardiac development Open Access

Abstract

The mitochondrial genome encodes thirteen proteins of the respiratory chain, which through oxidative phosphorylation produces most of the energy in adult cardiomyocytes. However, it is unclear what role mitochondria hold in the developing heart, which still depends heavily on anaerobic glycolysis for energy. Here, we investigate a possible connection between mitochondrial protein synthesis and cardiac morphogenesis by studying mice with systemic loss of the mitochondrial ribosomal protein MRPL40, a protein encoded in the critical deletion region of 22q11.2 deletion syndrome. While knockout of Mrpl40 was confirmed to be embryonically lethal, embryos with partial deletion of Mrpl40 exhibited survival and embryonic growth similar to wild-type embryos; however, these embryos also presented with ventricular septal defects. Additionally, we examined the cardiac phenotype of embryos with systemic partial deletion of both Mrpl40 and Slc25a1, another mitochondrial protein-encoding gene implicated in the cardiac presentation of 22q11.2 deletion syndrome. Interestingly, we observed a reduced prevalence of ventricular septal defects in embryos with the combined partial deletion when compared with embryos that exhibited partial deletion of either Mrpl40 or Slc25a1 alone. Taken together, our results demonstrate a potential role for MRPL40 in cardiac morphogenesis and suggest that combined partial deletion of Mrpl40 and Slc25a1 may be protective against the cardiac malformations observed in the single gene deletions.

Table of Contents

Introduction 1

Methods 15

Results 19

Discussion 25

References 29

About this Honors Thesis

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School	Emory College
Department	Biology
Degree	B.S.
Submission	Honors Thesis
Language	English
Research Field	Biology, Physiology Biology, General Biology, Genetics
Keyword	heart development mitochondria
Committee Chair / Thesis Advisor	Jennifer Kwong, Emory University
Committee Members	Victor Faundez, Emory University Leila Reider, Emory University

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