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Genetic models of Parkinson's disease.

In: Animal Models of Movement Disorders. Volume I. Berlin: Springer, 2011. 243-265 (Neuromethods ; 61)
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Parkinson’s disease (PD) is a chronic, progressive neurodegenerative movement disorder. To understand the pathomechanisms and to develop new drugs and therapies for PD, it is important to have animal models that recapitulate the slow progression and symptoms of the disease. The generation of genetic animal models of genes responsible for autosomal dominant but also autosomal recessive forms of PD has indeed accelerated our understanding of these pathomechanisms. To model the effect of dominant mutant alleles, transgenic mice were produced that express mutation-bearing proteins in neurons. To model lossof- function alleles, knockout mice were generated and studied. However, none of these models recapitulate PD disease as it occurs in PD patients. The latest mouse genetic technology may offer, at least in part, a relief for these challenges through the timed control of protein expression or gene knockout. Both can be achieved by the use of the Tamoxifen inducible CreERT2 gene switch that enables the inducible activation of transgene expression or inducible gene knockout. Thereby the CreERT2 system can be used to generate genetic models of gain-of-function (dominant) disease-associated alleles by the regulated expression of mutant coding regions as well as to model loss-of-function (recessive) disease-associated alleles by inducible gene knockout. In this chapter, we cover the design of such Tamoxifen inducible transgene constructs and the use of premade conditional knockout alleles generated by large-scale mutagenesis projects. Furthermore, we provide an overview of the available brain-specific CreERT2 mouse lines, notes on the control groups for inducible knockout experiments and a protocol for Tamoxifen administration.
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Publikationstyp Artikel: Sammelbandbeitrag/Buchkapitel
Schlagwörter Parkinson’s disease, Mouse model, Knockout, Transgenic, Tamoxifen
ISSN (print) / ISBN 1940-6045
ISBN 978-1-6177-9297-7
Bandtitel Animal Models of Movement Disorders. Volume I
Zeitschrift Neuromethods
Quellenangaben Band: 61, Heft: , Seiten: 243-265 Artikelnummer: , Supplement: ,
Verlag Springer
Verlagsort Berlin