Characterization of the cardiogenesis in embryos of a Gse-1tm-1a(EUCOMM)Wtsi mouse line

by Eva Baier
Doctoral thesis
Date of Examination:2021-08-05
Date of issue:2021-07-16
Advisor:Prof. Dr. Elisabeth Zeisberg
Referee:PD Dr. Jörg Männer
Referee:Prof. Dr. Bernd Wollnik
Persistent Address: http://dx.doi.org/10.53846/goediss-8738

 

 

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Abstract

English

HLHS is classified as a cyanotic heart disease, which accounts for 25% of all CHD mortalities. It is the leading cause of death in infants under the age of one year. One human candidate gene called KIAA00182 (Gse-1 in mice) was hypothesized to be implied in the pathogenesis of HLHS because of a) a de novo mutation of it, which was found in a child suffering from HLHS, and b) the documented lethality of homozygous Gse-1 mice by the age of three weeks. The objective of this study was to determine the timepoint of embryonic lethality of homozygous Tm-1a embryos and to identify a putative cardiac phenotype. The genotype of embryos at three embryonic ages (E11.5 p.c., E13.5 p.c. and E15.5 p.c.) was determined by PCR. The external morphology was inspected and assessed with a scoring system (external-phenotype score), which allowed a severity classification of external aberrancies. In two parts, the hearts of Tm-1a embryos were histologically analyzed, where part I focussed on the evaluation of non-ventricular structures. In part II, the quantitative assessment of the ventricular compact zone was performed. The quantification was further substantiated by the calculation of a ventricular reduction ratio, which reflects the degree of myocardial non-compaction. The discovery of biventricular non-compaction in homozygous E15.5 hearts constitutes the first description of a cardiac phenotype of the Gse-1 mouse line, which was identified as one element of aberrant pathogenesis that further appears to contribute to embryonic lethality of Tm-1a homozygosity.
Keywords: cardiogenesis; embryogenesis; GSE-1; noncompaction; hypoplastic left heart syndrome; cardiac development; cardiac phenotype; HLHS
 
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