In der vorliegenden Arbeit wurde das Mausgen mPet-1 als frühester,spezifischer Marker für die serotonerge Neuronen des Hirnstamms identifiziert und charakterisiert.Als Ets-Protein ist mPet-1 ein wHTH-Transkriptionsfaktor.Indem die codierende mPet-1 Sequenz unter die Kontrolle des Engrailed-1 Promoters gebracht wurde, konnte mPet-1 in Knock-In Experimenten ektopisch in der Mittel-/Hinterhirnregion exprimiert werden. Diese Experimente sollten Aufschluss darüber geben, ob mPet-1 serotonerge Neuronen induzieren kann. Heterozygote Mäuse zeigten keinen serotonergen Phänotyp. In der homozygoten Mutanten ist der Serotonintransporter ektopisch in der Pons induziert (n=1), jedoch nicht der Neurotransmitter (5-HT) und das zur 5-HT Synthese notwendige Enzym TpH. Diese Daten zeigen, dass mPet-1 in Abhängigkeit seiner Gendosis, der Region, und des genetischen Hintergrundes ausreicht, um den Serotonintransporter, aber nicht den kompletten serotonergen Neurotransmitterphänotyp zu induzieren.     «

In der vorliegenden Arbeit wurde das Mausgen mPet-1 als frühester,spezifischer Marker für die serotonerge Neuronen des Hirnstamms identifiziert und charakterisiert.Als Ets-Protein ist mPet-1 ein wHTH-Transkriptionsfaktor.Indem die codierende mPet-1 Sequenz unter die Kontrolle des Engrailed-1 Promoters gebracht wurde, konnte mPet-1 in Knock-In Experimenten ektopisch in der Mittel-/Hinterhirnregion exprimiert werden. Diese Experimente sollten Aufschluss darüber geben, ob mPet-1 serotonerge Neurone...     »

Serotonergic (5-hydroxytryptaminergic, 5-HT) neurons of the central nervous system play an important role in numerous physiological and behavioural functions in the adult mouse. In humans, dysfunction of the serotonergic system has ben implicated in various psychiatric disorders (e.g. depression, anxiety, schizophrenia). During development of the CNS the monoamine 5-HT has been shown to play crucial neuromodulatory roles such as induction of neurogenesis and neuronal differentiation. However, despite this importance of the central serotonergic neurotransmitter system, only little is known about the specification and development of these neurons. In mouse mPet-1 was identified. As an ETS-domain transcription factor it belongs to the winged helix family. mPet-1 is the earliest marker of the serotonergic neurons in the brain and preceedes the expression of the serotonin transporter (Sert). Therefore, we speculated that mPet-1 may be instrumentally involved in specification of these neurons. To test this hypothesis, we ectopically expressed mPet-1 in the mid-/hindbrain region using a knock-in approach in the Engrailed-1 (En-1) locus. The heterozygous En-1mPet-1/+ mice did not show any obvious serotonergic phenotype. Interestigly the analysis of the homozygous En-1mPet-1/mPet-1 Mutants displays an ectopic expression of the serotonin transporter (Sert) in the Pons, which is co-localized with ectopic mPet-1 expression. However, other terminal serotonergic markers, respectively the tryptophan hydroxylase (TpH) and the neurotransmitter itself (5-HT) are not induced at ectopic locations. Thus, our results suggest that mPet-1 in combination with still unknown regionspecific transcription factors is sufficient to induce Sert a major determinant of central 5-HT neurons in the Pons. However, mPet-1 is not sufficient to induce the complete 5-HT neuronal phenotyp.     «

Serotonergic (5-hydroxytryptaminergic, 5-HT) neurons of the central nervous system play an important role in numerous physiological and behavioural functions in the adult mouse. In humans, dysfunction of the serotonergic system has ben implicated in various psychiatric disorders (e.g. depression, anxiety, schizophrenia). During development of the CNS the monoamine 5-HT has been shown to play crucial neuromodulatory roles such as induction of neurogenesis and neuronal differentiation. However, de...     »