Transcript Role of Chromatin Remodeling Complexes during Aortic Valve

Chromatin Remodeling Complexes
in Heart Valve development
Maithri Sarangam
Summer 2012
Stankunas Lab
BAF Chromatin remodeling complex
Heart Valves
Significance
• Congenital heart valve defects affect significant portion of the
world population.
• Bicuspid aortic valve, affects
about 2% all people.
•
greatly increases risk for:
ventricular hypertrophy and
dilation, causing heart failure,
aortic aneurysms, and issues with
coronary vasculature
Conditional knockout of Brg1
NFATc1:Cre; BrgF/F
NFATc1:Cre; Brg F/+ (Wildtype)
NFATc1:Cre; Brg F/F (Mutant)
E14.5 Aortic valve phenotype
• Embryos harvested at E14.5
• “Thickened” leaflets
• Misshapen
• Accompanied by other
defects such as VSD and
misshapen pulmonic valves
16.5 valve 3D reconstruction
3D reconstruction
• There is a partial fusion
of leaflets 2 and 3.
• There is an increase in
volume that was not
observed in the other
phenotype
• Still unclear why there
seem to be different
phenotypes.
Mutant survival at 16.5
• Totals:
– 142 embryos, 131 live, 24 live mutants, 8 dead
mutants
• Frequencies:
– Theoretical mutant frequency: 25%
– Actual mutant frequency: 18.3%
dead mutants
–
= 25.0%
total mutants
Lincoln et. al, 2006
Molecular basis
Molecular Basis
Next Steps
• Continue to explore the molecular basis of the
phenotype, in embryonic mice, and adult
mice.
• Continue to examine matrix proteins, and
transcription factors.
Thank You!
• Professor Kryn Stankunas
• Brynn Simek
• Stankunas Lab
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Fern Bosada
Vidusha Devasthali
Ben Smood
Alex Akerberg
Cho Li
Alan Gomez
Scott Stewart