Robert Balza
BS Chemistry and Biology
Wisconsin Lutheran College
Project: Discerning the Role of SRF Through Loss-of-Function Analysis
Advisor: Dr. Ravi Misra
SRF is a member of the MADS (MCM1, Agamous, Deficiens, and SRF) box family of transcription factors.
Three key experimental observations have led us to hypothesize a central role for SRF in cardiogenesis.
First, the SRF binding elements of many cardiac specific gene promoters are crucial for their transcriptional regulation.
SRF target genes include cardiac structural protein isoforms such as actin and myosin, as well as physiological
proteins such as ANF, SERCA2 and NCX1. Second, the expression of SRF is enriched in the developing myocardium
during cardiogenesis. Third, SRF synergistically interacts with transcription factors known to be critical for
cardiogenesis, such as GATA-4, Nkx-2.5, and Myocardin. Collectively, these observations suggest an
important role for SRF in cardiac function and development. However, the precise role of SRF in cardiogenesis
remains undefined. Traditional loss-of-function techniques are inadequate to address the role of SRF in heart
development, since SRF knockout mice die prior to the onset of organogenesis. I propose to bypass this
embryonic lethal gastrulation defect with the use of a cardiac specific Cre-LoxP site-specific recombination
system. This system allows for the knockout of SRF specifically in cardiomyocytes.
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