TY  - JOUR
A1  - Liu, Ruiqi
A1  - Friedrich, Mike
A1  - Hemmen, Katherina
A1  - Jansen, Kerstin
A1  - Adolfi, Mateus C.
A1  - Schartl, Manfred
A1  - Heinze, Katrin G.
T1  - Dimerization of melanocortin 4 receptor controls puberty onset and body size polymorphism
JF  - Frontiers in Endocrinology
N2  - Xiphophorus fish exhibit a clear phenotypic polymorphism in puberty onset and reproductive strategies of males. In X. nigrensis and X. multilineatus, puberty onset is genetically determined and linked to a melanocortin 4 receptor (Mc4r) polymorphism of wild-type and mutant alleles on the sex chromosomes. We hypothesized that Mc4r mutant alleles act on wild-type alleles by a dominant negative effect through receptor dimerization, leading to differential intracellular signaling and effector gene activation. Depending on signaling strength, the onset of puberty either occurs early or is delayed. Here, we show by Förster Resonance Energy Transfer (FRET) that wild-type Xiphophorus Mc4r monomers can form homodimers, but also heterodimers with mutant receptors resulting in compromised signaling which explains the reduced Mc4r signaling in large males. Thus, hetero- vs. homo- dimerization seems to be the key molecular mechanism for the polymorphism in puberty onset and body size in male fish.
KW  - fluorescence lifetime imaging microscopy
KW  - Förster Resonance Energy Transfer
KW  - Mc4r
KW  - puberty
KW  - Xiphophorus
Y1  - 2023
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-354261
SN  - 1664-2392
VL  - 14
ER  - 
TY  - THES
A1  - Münch, Luca
T1  - Die Rolle transposabler Elemente in der Genese des malignen Melanom im Fischmodell Xiphophorus
T1  - The role of transposable elements in malignant melanoma development in the Xiphophorus fish model
N2  - Der Name der transposablen Elemente beruht auf ihrer Fähigkeit, ihre genomische Position verändern zu können. Durch Chromosomenaberrationen, Insertionen oder Deletionen können ihre genomischen Transpositionen genetische Instabilität verursachen. Inwieweit sie darüber hinaus regulatorischen Einfluss auf Zellfunktionen besitzen, ist Gegenstand aktueller Forschung ebenso wie die daraus resultierende Frage nach der Gesamtheit ihrer biologischen Signifikanz. Die Weiterführung experimenteller Forschung ist unabdingbar, um weiterhin offenen Fragen nachzugehen. Das Xiphophorus-Melanom-Modell stellt hierbei eines der ältesten Tiermodelle zur Erforschung des malignen Melanoms dar. Durch den klar definierten genetischen Hintergrund eignet es sich hervorragend zur Erforschung des bösartigen schwarzen Hautkrebses, welcher nach wie vor die tödlichste aller bekannten Hautkrebsformen darstellt. Die hier vorliegende Arbeit beschäftigt sich mit der Rolle transposabler Elemente in der malignen Melanomgenese von Xiphophorus.
N2  - The term “transposable elements” (TEs) is based on their ability to change their genomic position. Through insertions, deletions or chromosomal aberrations, their genomic mobility can cause genetic instability. The extent to which they further exert regulatory influence on cellular functions is the subject of current research, as is the resulting question of their overall biological significance. To further pursue these questions the continuation of experimental research is indispensable. In this regard, the Xiphophorus- melanoma-model represents one of the oldest animal models for the study of malignant melanoma. Thanks to its clearly defined genetic background, it is excellently suited for research into melanoma, which continues to be the most lethal of all known forms of skin cancer. The work presented here investigated the role of transposable elements in malignant melanomagenesis of Xiphophorus.
KW  - Transposon
KW  - Platy
KW  - Melanom
KW  - Überexpression
KW  - Schwertkärpfling
KW  - Expression
KW  - expression
KW  - Xiphophorus
KW  - xiphophorus
Y1  - 2023
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-289228
ER  -