A5013089574- Nitric Oxide and Endothelin Effects
- Phosphodiesterase function and regulation
- Receptor Mechanisms and Signaling
- Renin-Angiotensin System Studies
- Ion channel regulation and function
- Cell Adhesion Molecules Research
- Antiplatelet Therapy and Cardiovascular Diseases
- Atherosclerosis and Cardiovascular Diseases
- Cardiac electrophysiology and arrhythmias
- Neuroscience and Neuropharmacology Research
- Apelin-related biomedical research
- Platelet Disorders and Treatments
- Circadian rhythm and melatonin
- Lipid Membrane Structure and Behavior
- Complement system in diseases
- Glycosylation and Glycoproteins Research
- Ion Transport and Channel Regulation
- Liver Disease Diagnosis and Treatment
- Angiogenesis and VEGF in Cancer
- Cardiomyopathy and Myosin Studies
- Hemoglobinopathies and Related Disorders
- Pain Mechanisms and Treatments
- Laser Applications in Dentistry and Medicine
- Neuropeptides and Animal Physiology
- Ion Channels and Receptors
University of Tübingen
2014-2025
Bayer (Germany)
2024
St Vincents Institute of Medical Research
1996-2014
University of Lübeck
2013
Ludwig-Maximilians-Universität München
2003-2011
Center for Integrated Protein Science Munich
2011
University Medical Center
2011
Technical University of Munich
2003-2009
The University of Texas Southwestern Medical Center
2008
University of Regensburg
2007
Atherosclerosis is a widespread and devastating disease, but the origins of cells within atherosclerotic plaques are not well defined.To investigate specific contribution vascular smooth muscle (SMCs) to plaque formation by genetic inducible fate mapping in mice.Vascular SMCs were genetically pulse-labeled using tamoxifen-dependent Cre recombinase, CreER(T2), expressed from endogenous SM22α locus combined with Cre-activatable reporter genes that integrated into ROSA26 locus. Mature arterial...
Hyperpolarization-activated, cyclic nucleotide-gated cation currents, termed I f or h , are generated by four members of the hyperpolarization-activated, (HCN) channel family. These currents have been proposed to contribute several functions including pacemaker activity in heart and brain, control resting potential, neuronal plasticity. Transcripts HCN4 isoform found cardiomyocytes neurons, but physiological role this is unknown. Here we show that essential for proper function developing...
Malfunctions of potassium channels are increasingly implicated as causes neurological disorders. However, the functional roles large-conductance voltage- and Ca(2+)-activated K(+) channel (BK channel), a unique calcium, voltage-activated type have remained elusive. Here we report that mice lacking BK (BK(-/-)) show cerebellar dysfunction in form abnormal conditioned eye-blink reflex, locomotion pronounced deficiency motor coordination, which likely consequences learning deficiency. At...
Fumarates improve multiple sclerosis (MS) and psoriasis, two diseases in which both IL-12 IL-23 promote pathogenic T helper (Th) cell differentiation. However, show opposing responses to most established therapies. First, we humans that fumarate treatment induces IL-4–producing Th2 cells vivo generates type II dendritic (DCs) produce IL-10 instead of IL-23. In mice, fumarates also generate DCs induce vitro protect mice from experimental autoimmune encephalomyelitis. Type result...
Thrombosis and inflammation are intricately linked in several major clinical disorders, including disseminated intravascular coagulation acute ischemic events. The damage-associated molecular pattern molecule high-mobility group box 1 (HMGB1) is upregulated by activated platelets multiple inflammatory diseases; however, the contribution of platelet-derived HMGB1 thrombosis remains unexplored. Here, we generated transgenic mice with platelet-specific ablation determined that a critical...
Background— Abnormally elevated blood pressure is the most prevalent risk factor for cardiovascular disease. The large-conductance, voltage- and Ca 2+ -dependent K + (BK) channel has been proposed as an important effector in control of vascular tone by linking membrane depolarization local increases cytosolic to hyperpolarizing outward currents. However, BK may also affect regulating salt fluid homeostasis, particularly adjusting renin-angiotensin-aldosterone system. Methods Results— Here we...
X-linked retinoschisis (XLRS) is the most common cause of juvenile macular degeneration in males, resulting vision loss early life. The gene involved XLRS was identified recently. It encodes a protein with disoidin domain, suggested to be cell-cell interactions. We have screened for mutations 234 familial and sporadic cases 82 different 214 (91%). Thirty one were found more than once, i.e. 2–10 times, exception 214G→A mutation which 34 apparently unrelated cases. origin patients, linkage...
The current management of patients with stroke intravenous thrombolysis and endovascular thrombectomy is effective only when it timely performed on an appropriately selected but minor fraction patients. development novel adjunctive therapy highly desired to reduce morbidity mortality stroke. Since endothelial dysfunction implicated in the pathogenesis featured suppressed nitric oxide synthase (eNOS) concomitant deficiency, restoring represents a promising approach treating injury.
The molecular basis for cerebellar plasticity and motor learning remains controversial. Cerebellar Purkinje cells (PCs) contain a high concentration of cGMP-dependent protein kinase type I (cGKI). To investigate the function cGKI in long-term depression (LTD) learning, we have generated conditional knockout mice lacking selectively PCs. These mutants had normal morphology intact synaptic calcium signaling, but strongly reduced LTD. Interestingly, no defects general behavior performance could...
The function of cytoskeletal proteins in the modulation vascular smooth muscle cell (SMC) phenotype during disease is poorly understood. In this report, we used a combination gene targeting and Cre/lox-mediated fate mapping mice to investigate role SM22α, an SMC-specific protein unknown function, development atherosclerosis. hypercholesterolemic ApoE-deficient mice, genetic ablation SM22α resulted increased atherosclerotic lesion area higher proportion proliferating SMC-derived plaque cells....
To explore the functional significance of cGMP-dependent protein kinase type I (cGKI) in regulation erythrocyte survival, gene-targeted mice lacking cGKI were compared with their control littermates. By age 10 weeks, cGKI-deficient exhibited pronounced anemia and splenomegaly. Compared mice, mutants had significantly lower red blood cell count, packed volume, hemoglobin concentration. Anemia was associated a higher reticulocyte number an increase plasma erythropoietin The spleens mutant...
Smooth muscle expresses the Ialpha and Ibeta isoforms of cGMP-dependent protein kinase I (cGKI). Inactivation murine cGKI gene prkg1 leads to multiple phenotypes premature death at approximately 6 weeks. We reconstituted mice with cGKIalpha or -Ibeta isozyme test which was needed support basic smooth functions. Mice were generated by targeting. The coding sequences placed under control SM22alpha promoter express either isoform selectively in cells (SM-Ialpha SM-Ibeta transgene). To generate...
Synaptic long-term potentiation (LTP) at spinal neurons directly communicating pain-specific inputs from the periphery to brain has been proposed serve as a trigger for pain hypersensitivity in pathological states. Previous studies have functionally implicated NMDA receptor-NO pathway and downstream second messenger, cGMP, these processes. Because cGMP can broadly influence diverse ion-channels, kinases, phosphodiesterases, pre- well post-synaptically, precise identity of targets mediating...
Cyclic GMP (cGMP) is an important intracellular signaling molecule in the cardiovascular system, but its spatiotemporal dynamics vivo largely unknown.To generate and characterize transgenic mice expressing fluorescence resonance energy transfer-based ratiometric cGMP sensor, indicator with EC50 of 500 nmol/L (cGi500), tissues.Mouse lines smooth muscle-specific or ubiquitous expression cGi500 were generated by random transgenesis using SM22α promoter fragment targeted integration a Cre...
Sildenafil, an inhibitor of the cGMP-degrading phosphodiesterase 5 that is used to treat erectile dysfunction, has been linked increased risk melanoma. Here, we have examined potential connection between cGMP-dependent signaling cascades and melanoma growth. Using a combination biochemical assays real-time monitoring cells, report growth-promoting pathway in murine human cells. We document C-type natriuretic peptide (CNP), ligand membrane-bound guanylate cyclase B, enhances activity protein...
Gap junctions are characteristically increased in the myometrium during term and preterm delivery thought to be essential for development of uterine contractions labour. Expression connexin43 (Cx43), major myometrial gap junction protein, is delivery. We have generated a mouse mutant (Cx43fl/fl:SM-CreERT2), which coding region Cx43 can specifically deleted smooth muscle cells at any given time point by application tamoxifen. By this approach, we were able study long-term effects on functions...
ABSTRACT Mice deficient in the smooth muscle Ca v 1.2 calcium channel (SMACKO, α 1c ‐ subunit knockout) have a severely reduced micturition and an increased bladder mass. L‐type current, protein, spontaneous contractile activity were absent of SMACKO mice. K + carbachol (CCh)‐induced contractions to 10‐ fold detrusor muscles from The dihydropyridine isradipine inhibited CCh‐induced CTR but had no effect contraction was blocked by removing extracellular 2+ unaffected PLC inhibitor U73122 or...
Cardiac atrial natriuretic peptide (ANP) locally counteracts cardiac hypertrophy via the guanylyl cyclase-A (GC-A) receptor and cGMP production, but downstream signalling pathways are unknown. Here, we examined influence of ANP on β-adrenergic versus Angiotensin II (Ang II)-dependent (Gs vs. Gαq mediated) modulation Ca2+ i-handling in cardiomyocytes intact hearts. L-type currents i transients adult isolated murine ventricular myocytes were studied by voltage-clamp recordings fluorescence...
The hyperpolarization-activated current I(h) that is generated by cyclic nucleotide-gated channels (HCNs) plays a key role in the control of pacemaker activity sinoatrial node cells heart. By contrast, it unclear whether also relevant for normal function cardiac ventricles.To study HCN3-mediated component ventricular function.To test hypothesis HCN3 regulates action potential waveform, we have and analyzed HCN3-deficient mouse line. At basal heart rate, mice deficient displayed profound...