of the Max - MDC

Structure of the Group
Group Leader
Prof. Dr. Michael Bader
Scientists
Dr. Natalia Alenina
Dr. Philipp Boyé*
Dr. Jens Buttgereit
Dr. Cibele Cardoso*
Dr. Robert Fischer
Dr. Franziska Hampich
Dr. Alexander
Krivokharchenko
Dr. Irina Lapidus*
Dr. Vanessa Merino*
Dr. Marcelo Mori*
Dr. Elena Popova
Dr. Fatimunnisa Qadri
Dr. Regiane Sabatini*
Dr. Edson Santos*
Dr. Tanja Shmidt
Dr. Gabin Sihn*
Dr. Mihail Todiras*
Dr. Martin Würtele*
Graduate Students
Marcos Barbosa*
Saleh Bashammakh
Celine Burckle*
Aline Hilzendeger*
Dana Kikic
Katarina Kotnik
Markus May*
Anna Panek
Brit Rentzsch
Michael Ridders*
Ines Schadock
Stefanie Schultrich*
Katja Tenner
Larissa Vilianovich
Ping Xu
Technical Assistants
Adelheid Böttger*
Sabine Grüger
Andrea Müller
Monika Nitz*
Irene Strauss
Lieselotte Winkler*
Susanne Wollenzin*
Secretariat
Dana Lafuente*
Iris Apostel-Krause*
* part of the period reported
WT
TGR
Cardiac hypertrophy in
NPR-B∆KC-transgenic rats.
Transgenic overexpression of
a deletion mutant of the
natriuretic peptide receptor
NPR-B lacking most of the
cytoplasmic domain leads to
left ventricular hypertrophy
of transgenic (TGR) rats vs.
wild-type controls (WT).
One focus of our serotonin research is its role in development
and differentiation. In TPH1-deficient mice, the usedependent
remodelling of the mammary gland and liver
regeneration after hepatectomy or hypoxia are severely
impaired by the lack of platelet serotonin. Furthermore, we
are interested in the development of the serotonergic system.
In order to detect crucial molecules for the development
of serotonergic neurons, mouse ES cells are genetically
modified and selected during in vitro differentiation to
enrich for serotonergic precursors.
Transgenic and stem cell technology
Alexander Krivokharchenko, Elena Popova, Irina Lapidus,
Natalia Alenina, Katarina Kotnik, Larissa Vilianovitch
Serotonin system
Natalia Alenina, Dana Kikic, Katja Tenner, Katarina
Kotnik, Saleh Bashammakh, Martin Würtele
Serotonin is at the same time a very important neurotransmitter
in the brain and a major peripheral mediator produced
by enterochromaffin cells of the gut and transported
and released by platelets in the circulation. After our discovery
of the second serotonin synthesizing enzyme, tryptophan
hydroxylase 2 (TPH2), which is responsible for serotonin
synthesis in the central nervous system, we could
show that this gene shows linkage to psychiatric diseases.
Mice deficient in TPH1, the isoform responsible for the synthesis
of serotonin in the gut, exhibited defects in platelet
aggregation due to a blunted release of a-granules containing
von Willebrand factor at sites of vessel injury. We could
show that serotonin stimulates the release of a-granules by
being covalently linked to glutamine residues of small
GTPases. These findings were the basis of a novel concept of
signalling (serotonylation, monoaminylation), which may
be employed by all monoaminergic hormones, such as serotonin,
dopamine, and norepinephrine, and does not involve
classical receptors but intracytoplasmic transglutamination.
TPH1-deficient mice are ideal models to study the peripheral
actions of serotonin, since they are devoid of platelet
serotonin. Besides the antithrombotic phenotype, these
mice show alterations in the immune and cardiovascular
system including a protection against pulmonary hypertension,
but they unexpectedly have a normal gut function.
The group is also interested to develop transgenic and stem
cell technology in the mouse and even more importantly in
the rat. In order to allow targeted genetic alterations in the
rat, several techniques are being employed: Rat ES cells
were isolated but did not allow germline transmission.
Therefore, nuclear transfer technologies have been developed
and optimized for the rat. Furthermore, transgenic
rats have been produced carrying constructs, which express
small interference RNAs suited to downregulate specific
genes.
Selected Publications
Cayla, C, Todiras, M, Iliescu, R, Gross, V, Pilz, B, Chai, GX, Saul, V,
Merino, VF, Pesquero, JB, Baltatu, O, Bader, M. (2007) Mice deficient
for both kinin receptors are normotensive and protected
from endotoxin-induced hypotension. FASEB J. 21, 1689-1698
Langenickel, TH, Buttgereit, J, Pagel-Langenickel, I, Lindner, M,
Monti, J, Beuerlein, K, Al-Saadi, N, Plehm, R, Popova, E, Tank,
J, Dietz, R, Willenbrock, R, Bader, M. (2006). Cardiac hypertrophy
in transgenic rats expressing a dominant-negative mutant
of the natriuretic peptide receptor B. Proc. Natl. Acad. Sci. USA
103, 4735-4740.
Lesurtel, M, Graf, R, Aleil, B, Walther, DJ, Tian, Y, Jochum, W,
Gachet, C, Bader, M, Clavien, PA. (2006). Platelet-derived
serotonin mediates liver regeneration. Science 312, 104-107.
Popova, E, Bader, M, Krivokharchenko, A. (2006) Full-term
development of rat after transfer of nuclei from two-cell stage
embryos. Biol Reprod 75, 524-530
Maul, B, Siems, WE, Krause, W, Pankow, A, Becker, M,
Gembardt, F, Alenina, N, Walther, T, Bader, M. (2005) Central
angiotensin II controls alcohol consumption via its AT1 receptor.
FASEB J. 19, 1474-1481
12 Cardiovascular and Metabolic Disease Research