Mouse model of the human serotonin transporter-linked polymorphic region


Por: Piszczek L, Memoli S, Raggioli A, Viosca J, Rientjes J, Hublitz P, Czaban W, Wyrzykowska A and Gross C

Publicada: 1 dic 2019 Ahead of Print: 30 oct 2019
Categoría: Genetics

Resumen:
Genetic factors play a significant role in risk for mood and anxiety disorders. Polymorphisms in genes that regulate the brain monoamine systems, such as catabolic enzymes and transporters, are attractive candidates for being risk factors for emotional disorders given the weight of evidence implicating monoamines involvement in these conditions. Several common genetic variants have been identified in the human serotonin transporter (5-HTT) gene, including a repetitive sequence located in the promoter region of the locus called the serotonin transporter-linked polymorphic region (5-HTT-LPR). This polymorphism has been associated with a number of mental traits in both humans and primates, including depression, neuroticism, and harm avoidance. Some, but not all, studies found a link between the polymorphism and 5-HTT levels, leaving open the question of whether the polymorphism affects risk for mental traits via changes in 5-HTT expression. To investigate the impact of the polymorphism on gene expression, serotonin homeostasis, and behavioral traits, we set out to develop a mouse model of the human 5-HTT-LPR. Here we describe the creation and characterization of a set of mouse lines with single-copy human transgenes carrying the short and long 5-HTT-LPR variants. Although we were not able to detect differences in expression between the short and long variants, we encountered several technical issues concerning the design of our humanized mice that are likely to have influenced our findings. Our study serves as a cautionary note for future studies aimed at studying human transgene regulation in the context of the living mouse.

Filiaciones:
Piszczek L:
 Epigenetics and Neurobiology Unit, European Molecular Biology Laboratory, EMBL Rome, Monterotondo, Italy

 Research Institute of Molecular Pathology, Vienna, Austria

Memoli S:
 Epigenetics and Neurobiology Unit, European Molecular Biology Laboratory, EMBL Rome, Monterotondo, Italy

Raggioli A:
 Epigenetics and Neurobiology Unit, European Molecular Biology Laboratory, EMBL Rome, Monterotondo, Italy

:
 Epigenetics and Neurobiology Unit, European Molecular Biology Laboratory, EMBL Rome, Monterotondo, Italy

 Promotion of Health and Biomedical Research in the Valencian Region (FISABIO), Valencia, Spain

Rientjes J:
 Monash Genome Modification Platform (MGMP), Monash University, Clayton, Australia

Hublitz P:
 Epigenetics and Neurobiology Unit, European Molecular Biology Laboratory, EMBL Rome, Monterotondo, Italy

 MRC Weatherall Institute of Molecular Medicine, University of Oxford, Oxford, UK

Czaban W:
 Epigenetics and Neurobiology Unit, European Molecular Biology Laboratory, EMBL Rome, Monterotondo, Italy

Wyrzykowska A:
 Epigenetics and Neurobiology Unit, European Molecular Biology Laboratory, EMBL Rome, Monterotondo, Italy

Gross C:
 Epigenetics and Neurobiology Unit, European Molecular Biology Laboratory, EMBL Rome, Monterotondo, Italy.
ISSN: 14321777





MAMMALIAN GENOME
Editorial
Springer Verlag, 233 SPRING ST, NEW YORK, NY 10013 USA, Estados Unidos America
Tipo de documento: Article
Volumen: 30 Número: 11-12
Páginas: 319-328
WOS Id: 000508564600001
ID de PubMed: 31667540
imagen Open Access

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