geneti

Projekttitel
Etablierung und Charakterisierung osteoporotischgenetischer Tiermodelle
Projektbeschreibung
Establishment and characterization of transgenic animal models of
osteoporosis
The project is a part of the trans-regional collaborative research center
(SFB/Transregio 79). The project (T1) aims to accomplish two parallel
goals: 1. to produce transgenic rat models exhibiting an osteoporotic
phenotype and 2. Using next generation sequencing on conventionally
induced osteoporotic rat model (i.e. ovariectomy and deficient diet) to
identify new candidate genes involved in the multi-factorial disease. The
first goal arises from the need for a reliable animal model with a
reproducible osteoporotic phenotype to develop and understand the
osseointegration and degredation of biomaterials in the musculoskeletal
system. Therefore, Inhibitors of the Wnt signaling pathway, sclerostin
(SOST) or Dickkopf-1 (DKK-1) will be over-expressed in the rat. The gene
choice came from a clearly defined pathophysiological alteration that was
already described in mouse model and demonstrated an inhibition of bone
formation and consequent osteoporotic phenotype. Nonetheless, the
project will provide the first SOST- and DKK-1 transgenic rats for
translational studies after characterization. Further, inhibitory antibodies
against SOST and DKK-1 are to be used as therapeutic approach to
neutralize their over-expression in the transgenic rat model, and thus
enhance bone formation.
However, the goal of identifying new candidate genes in a rat model with
conventionally induced osteoporosis using ovariectomy and multi deficient
diet. This shall help understanding the exact molecular mechanisms which
are yet to explore. This goal will be attempted after further optimization of
this model using Next Generation sequencing methodology. Therefore
differential expression profiling will be investigated to identify potential
new candidate genes. Afterwards, in vitro testing shall help decide
whether a new transgenic rat model of the new candidate gene could be
generated.
Projektleitung
Prof. Christian Heiß
Tel.: +49-(0)-641-98544601
[email protected]
EINRICHTUNG
Universitätsklinikum Gießen und Marburg GmbH, Standort Gießen
INSTITUT
Klinik und Poliklinik für Unfall-, Hand- und Wiederherstellungschirurgie Operative Notaufnahme, Labor für experimentelle Unfallchirurgie JustusLiebig-Universität Gießen
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Weitere Projektmitglieder
Dr. Thaqif El Khassawna Fachbereich Medizin (FB11) Labor für
experimentelle Unfallchirurgie Justus-Liebig Universität Gießen Kerkraderstr.
9 35394 Gießen Tel.: 0641/9433-118 FAX: 0641/9433-119
[email protected]
Laufzeit des Projektes
01.07.2014
01.07.2018
Mittelgeber
DFG
Online-Information
https://www.unigiessen.de/cms/fbz/fb11/institute/klinik/chirurgie/uch/forschung/sfb-trr79
Forschungsbereich
Grundlagenforschung
Publikationen
[1] El Khassawna T, Bocker W, Govindarajan P, Schliefke N, Hurter B,
Kampschulte M, Schlewitz G, Alt V, Lips KS, Faulenbach M, Mollmann
H, Zahner D, Durselen L, Ignatius A, Bauer N, Wenisch S, Langheinrich
AC, Schnettler R, Heiss C. Effects of multi-deficiencies-diet on bone
parameters of peripheral bone in ovariectomized mature rat. PLoS One
2013;8: e71665.
[2] Bauer NB, Khassawna TE, Goldmann F, Stirn M, Ledieu D, Schlewitz
G, Govindarajan P, Zahner D, Weisweiler D, Schliefke N, Bocker W,
Schnettler R, Heiss C, Moritz A. Characterization of bone turnover and
energy metabolism in a rat model of primary and secondary
osteoporosis. Exp Toxicol Pathol 2015;67: 287-96.
[3] Bocker W, El Khassawna T, Bauer N, Brodsky K, Weisweiler D,
Govindarajan P, Schlewitz G, Kampschulte M, Durselen L, Thormann U,
Szalay G, Schnettler R, Langheinrich AC, Heiss C. Short-term
glucocorticoid treatment causes spinal osteoporosis in ovariectomized
rats. Eur Spine J 2014.
[4] El Khassawna T, Böcker W, Brodsky K, Weisweiler D, Govindarajan
P, Kampschulte M, Thormann U, Henss A, Rohnke M, Bauer N, Müller R,
Deutsch A, Ignatius A, Dürselen L, Langheinrich A, Lips K, Schnettler
R, Heiss C. Impaired extracellular matrix structure resulting from
malnutrition in ovariectomized mature rats. Histochemistry and Cell
Biology 2015: 1-17.
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