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Dissertation zugänglich unter
URN: urn:nbn:de:gbv:18-47504
URL: http://ediss.sub.uni-hamburg.de/volltexte/2010/4750/


Morphological characterization of Estrogen-Related Receptor gamma deficient mice

Morphologische Charakterisierung des Estrogen-Related Receptors gamma Mausmodels

Ganos, Christos

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Freie Schlagwörter (Englisch): Estrogen-Related Receptor gamma , Knock-out mice , Dystonia , Movement Disorders
Basisklassifikation: 44.35 , 44.34 , 44.90 , 44.48
Institut: Medizin
DDC-Sachgruppe: Medizin, Gesundheit
Dokumentart: Dissertation
Hauptberichter: Schumacher, Udo (Prof. Dr.)
Sprache: Englisch
Tag der mündlichen Prüfung: 16.07.2010
Erstellungsjahr: 2010
Publikationsdatum: 24.08.2010
Kurzfassung auf Deutsch: Medizinische Genetik.
Anatomie.
Histologie.
Neurologie.
Kurzfassung auf Englisch: Introduction: The family of orphan nuclear receptors comprises ligand-independent intracellular and/or intranuclear transcription factors, which play several roles in basic physiological functions including cell metabolism, differentiation and growth. The last orphan nuclear receptor identified was the estrogen-related receptor (ERR) gamma. Its role in determining morphological and phenotypical properties was examined in the present study using knockout mice.

Materials & Methods: Tissues of ERR gamma -/- mice generated from embryonic stages to adulthood were histologically analysed after genotypic analysis. Immunohistochemistry was also used. Morphometric analysis was employed to quantify the total and regional brain size of the phenotypes.

Results: We found that ERR gamma -/- were underrepresented in the postnatal phase indicating to an increased lethality of the phenotype allowing only <1% of the mice to reach adult age. A significant reduction in body weight (41.2% for adult mice) beginning from P1 was observed and a reduction in vertex-breech length (12.7% for adult mice) was noted in the surviving mice. The mice demonstrated dystonic hind-limb reactions leading to tremorous circling body movements (waltzing) and retropulsion. On gross morphological organ examination, the brain and the stomach were altered. The telencephalic region of the ERR gamma -/- brain was dorsally shortened, with the lamina quadrigemina protruding to a greater extend between the telencephalon and the cerebellum. The mesencephalic tegmentum of the ERR gamma -/- mice was significantly larger and the cerebellum smaller (normalized values to the absolute brain size of each genotype) compared to their wildtype and heterozygous littermates. The wall of the stomach of the ERR gamma -/- mice was thickened with protruding bulgy masses, representing glandular hypertrophy with mononuclear cell infiltration.

Conclusions: These results support the hypothesis that the ERR gamma receptor plays a key role in neurogenesis and neuronal migration, leading to regional brain disproportionality causing a morphological and functional disruption between the cerebellum and the basal ganglia. They also highlight the suppressive effect of ERR gamma -/- on cell proliferation in the stomach leading to glandular hyperplasia if absent.

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