Research Report 2010 - MDC

Mineralocorticoid receptorAnette FiebelerScientists and studentsAtakan AydinCarsten LindschauPhilipp MaassCosima SchmidtAnne KonkelMichael OechsnerAndrey da Costa-GoncalvesTechnical AssistantsAstrid MühlEireen KleinIrene HolfingerYvette NeuenfeldChristel AndréeRamona ZummachIlona KamerFigure 1. Type E brachydactyly, balancedtranslocation t(8;12)(q13;p11.2)in Metaphase-FISH, fibroblasts transformedto chondrogenic cells, upregulationof Indian hedgehog (IHH) anddownregulation of parathyroid-likehormone (PTHLH).generally associated with regulatory activity. Our findingshave broader implications for understanding howchromosomal aberrations affect epigenetic modificationsand long-range gene regulation. The results indicatethat dysregulation of chondrogenesis due to anovel site for interaction of AP1 and ETS1 upstream ofPTHLH, is the underlying cause for the BDE.That is all very nice but it’s miceVolkmar Gross and Friedrich C. Luft have been collaboratorsfor almost 20 years. They have maintained thestandard of conservative cardiovascular physiology asopposed to descriptive RT-PCR, RNase protectionassays, and Western blotting (where physiology ends bythe others), although we have incorporated all thesetechniques to test our hypotheses. Our goal is to showit at the experimental level, gene expression can be nosubstitute. Gross and Luft have attempted to bring allof cardiovascular physiology to mice and particularly tounique mice. Recently, we investigated synophilin (acollaboration with Paul Greengard, Nobel Prize 2000).The spinophilin protein controls intensity/duration of Gprotein-coupled receptor signaling and thereby influencessynaptic activity. We hypothesized thatspinophilin affects blood pressure through centralmechanisms. We measured blood pressure and heartrate in SPL-deficient -/-, SPL+/-, and SPL +/+ mice bytelemetry combined with fast Fourier transformation.We found that an increase in central sympathetic outflowparticipates in blood pressure and heart rateincreases in SPL -/- mice. The elevated blood pressure inSPL(-/-) mice was associated with attenuated baroreflexsensitivity and decreased parasympathetic activity.Our study is the first to show a role for the spinophilingene in blood pressure regulation. These novel resultshave a bearing on centrally (brain) mediated control ofblood pressure. The group has pursued additionalmouse-related projects. These include work on db/dbleptin receptor deficient mice and mice deficient in thesolulble epoxide hydrolase.Mineralocortcoid receptor signalingAnnete Fiebeler has led a group of investigators specificallyinterested in mineralocorticodi-reseceptor signaling.In a recent study, she and friends showed that corticosteroneinduces rapid mineralocorticoid receptorCardiovascular and Metabolic Disease Research 33